Refresh: Pathology

Undergraduate Pathology Series
Refresh
Pathology
1st Edition
High-Yield Exam Oriented Review for MBBS
Dr. Shiva M.D.

Undergraduate Pathology Series 2
Refresh Pathology
1st edition: January, 2018
Dr. Shiva M.D. (Pathology)
Dedicated to Dr. G. Taraka Rajaram MS
E-mail: drshivav@gmail.com
Facebook: www.facebook.com/UndergraduatePathology/
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Refresh Pathology, 1st Edition - Dr. Shiva M.D. 3
Contents
Paper I (General Pathology & Hematology)
1) Cellular Responses to Stress and Toxic Insults:

Adaptation, injury, and Death, 6
2) Inflammation and Repair, 13
3) Hemodynamic Disorders, Thromboembolic Disease, and Shock, 23
4) Genetic Disorders, 30
5) Diseases of the Immune System, 33
6) Neoplasia, 40
7) Infectious Diseases, 47
8) Environmental and Nutritional Diseases, 55
9) Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, 59
10) Red Blood Cell Disorders, 68
11) Bleeding Disorders, 76
** Miscellaneous, 81
Paper II (Systemic Pathology)
12) Blood Vessels, 83

13) The Heart, 87
14) The Lung, 94
15) Head and Neck, 101
16) The Gastrointestinal Tract, 103
17) Liver and Gallbladder, 110
18) The Pancreas, 116
19) The Kidney, 118
20) The Lower Urinary Tract and Male Genital System, 126
21) The Female Genital Tract, 130
22) The Breast, 137
23) The Endocrine System, 143
24) The Skin, 149
25) Bones, Joints, and Soft Tissue Tumors, 152
26) The Central Nervous System, 156
** Miscellaneous, 160
There are two kinds of students! Those who utilize their

capabilities, and those who don’t!
I believe, great teachers exist, just because of great

students!
Dr. Shiva M.D.

PAPER I
GENERAL PATHOLOGY
& HEMATOLOGY
1. Cellular Responses to Stress and Toxic Insults:

Adaptation, injury, and Death
4 Marks
1) Tabulate differences between necrosis and degeneration. (Feb. 2017)

2) Mechanisms of apoptosis. (Jan. 2015)
3) Tabulate the differentiating features of Necrosis and Apoptosis. (Jan. 2014)
4) Free radicles. (July, 2013)
5) Contrasting features of apoptosis and necrosis. (March, 2010)
6) Metaplasia. (Aug. 2009)
7) Necrosis. (Feb. 2009)
8) Gangrene. (Oct. 2008)
9) Fatty Liver. (Sep/Oct. 2007)
10) Free radicles and cell injury. (May, 2007)
11) Role of free radicles in cell injury. (Oct. 2004)
12) Apoptosis. (April/May, 2004)
13) Pathological calcification. (Sep. 2003)
2 Marks
1) Name four types of necrosis with one example each. (July, 2016)
2) List any four types of necrosis with one example each. (Jan. 2016)
3) What are the special stains for fat? (Jan. 2016)
4) Define apoptosis and mention any two morphological features. (July, 2015)
5) Four examples of hyperplasia. (Jan. 2015)
6) Lipofuscin. (July, 2013)
7) Name 4 morphologic changes (cytoplasmic & nuclear) in necrotic cell. (Jan. 2013)
8) Name four (4) types of necrosis with examples. (July, 2012)
9) Name four (4) fat stains. (July, 2012)
10) Autophagy. (Jan. 2012)
11) Hypertrophy and Hyperplasia. (July, 2011)
12) Pathogenesis of dystrophic calcification. (Jan. 2011)
13) Taby cat appearance of heart (Tigered effect). (March. 2010)
14) Metaplasia. (Feb. 2009)
15) Metaplasia. (May, 2006)
16) Atrophy. (March/April, 2005)
17) Role of free radicles in cell injury. (Oct. 2004)
Hypertrophy
Def.: An increase in the size of cells, leading to increase in the size of the affected organ.
Mechanisms: Increased cellular proteins
Association: May coexist with hyperplasia.
Types with e.g.,: I) Physiologic hypertrophy: Hypertrophy of skeletal muscle with increased
work load in bodybuilders; Hypertrophy of smooth muscle of uterus during pregnancy.
II) Pathologic hypertrophy: Hypertrophy of cardiac muscle due to chronic hemodynamic
overload with hypertension.
Hyperplasia
Def.: An increase in the number of cells in an organ or tissue, leading to their enlargement.
Mechanisms: Growth factor driven proliferation
Association: May coexist with hypertrophy
Types with e.g.,: I) Physiologic hyperplasia: Hyperplasia of glandular elements of breast
during puberty & pregnancy; Hyperplasia of hepatocytes following hepatic damage or
resection.
II) Pathologic hyperplasia: Endometrial hyperplasia; Benign prostatic hyperplasia
Atrophy
Def.: Decrease in cell size causing a reduction in the size of tissue or organ.
Mechanisms: Decreased protein synthesis & increased protein degradation in cells
Types with e.g.,: I) Physiologic atrophy: Atrophy of embryonic structures like notochord
during fetal development; Atrophy of endometrium & breast after menopause.
II) Pathologic atrophy:
1) Atrophy of disuse: Skeletal muscle atrophy following immobilization
2) Denervation atrophy: Atrophy of skeletal muscle due to damage to nerve supply
3) Ischemic atrophy: Tissue atrophy with diminished blood supply
4) Pressure atrophy: Tissue compression may cause atrophy.
Comp.: Death by apoptosis
Metaplasia
Def.: Replacement of one differentiated cell type with another cell type.
Mechanisms: Reprogramming of stem cells, existing in normal tissues, or of undifferentiated
mesenchymal cells present in connective tissue.
Types with e.g.,:
I) Epithelial metaplasia: 1) Squamous metaplasia (MC): With cigarette smoking, normal
ciliated columnar epithelial lining of airways is replaced with stratified squamous epithelium.
With stones in excretory ducts of salivary glands or pancreas, normal columnar lining is
replaced with stratified squamous epithelium.
2) Columnar metaplasia: With chronic GERD, squamous epithelium of esophagus is
replaced with intestinal-like columnar cells (Barrett esophagus).
Comp.: Dysplasia; Malignant transformation
II) Connective tissue metaplasia: Formation of mesenchymal elements (cartilage, bone or

adipose tissue) in tissues that do not contain them. E.g., Bone formation in muscle (myositis
ossificans) following intramuscular hemorrhage.
Free Radicals
Source: Oxygen derived (ROS) or nitrogen oxide derived.
Reactive oxygen species: Hydrogen peroxide, superoxide anion & hydroxyl ions.
Production of free radicals:
1) Reduction-oxidation reactions that occur during normal metabolic processes, such as
mitochondrial respiration.
2) Absorption of radiant energy (UV light, X-rays)
3) During inflammation, by neutrophils & macrophages
4) Transition metals (iron & copper) can catalyze free radical formation.
Removal of free radicals:
1) Antioxidants either block free radical formation or inactivate them. e.g., Vit. A, E & C
2) Enzymes such as catalase, superoxidase dismutase, & glutathione peroxidase break down
hydrogen peroxide & superoxide anions.
Oxidative stress: State of excess free radicles with increased production or decreased
removal of ROS.
Pathologic effects:
1) Lipid peroxidation in membranes, causing extensive membrane damage.
2) Oxidative modification of proteins, causing cellular damage.
3) Damage to DNA, may promote cell aging & malignant transformation.
Necrosis
“Spectrum of the morphologic changes that follow cell death in living tissue or organs.”
Mechanisms: 1) Denaturation of intracellular proteins
2) Enzymatic digestion of the injured cell
Morphology:
Cytoplasm: Increased eosinophilia & glassy or vacuolated appearance.
Nuclear changes: 1) Pyknosis: Small, dense nucleus
2) Karyorrhexis: Fragmented nucleus
3) Karyolysis: Faint, dissolved nucleus
Types
I) Coagulative necrosis
Cause: Ischemia involving all the organs except brain.
Morphology: Gross Firm
Micro. Preserved architecture with eosinophilic, anucleate cells
Infarct: A localized area of coagulative necrosis
Fate: Phagocytosis with inflammatory response
II) Liquefactive necrosis

Cause: Ischemia involving brain; Bacterial infections.
Morphology: Formation of liquid viscous mass with inflammatory response.
Pus: Creamy yellow exudate seen with pyogenic bacterial infections.
III) Gangrenous necrosis
Cause: Loss of blood supply
Site: Limbs (MC-Lower limb)
Morphology Coagulative necrosis (dry gangrene) or liquefactive necrosis with superimposed
bacterial infections (wet gangrene)
IV) Caseous necrosis
Cause: Tuberculosis
Morphology: Gross friable white appearance
Micro. Collection of fragmented cells & amorphous granular debris with granulomatous
inflammatory response.
V) Fat necrosis
Cause: Acute pancreatitis
Morphology: Gross Chalky-white areas (fat saponification)
Micro. Foci of necrotic fat cells & deposited calcium salts with inflammatory response.
VI) Fibrinoid necrosis
Cause:
Mechanism: Deposition of immune complexes with fibrin
Morphology: Wall of arteries show bright pink & amorphous appearance.
Fate: Elimination of necrotic tissue by leukocytes. Dystrophic calcification may occur with
incomplete removal.
Apoptosis
“A pattern of cell death in which cells activate enzymes that degrade the cells own nuclear
DNA and nuclear & cytoplasmic proteins.”
Causes
Physiologic (MC)
1) Programmed destruction of cells during embryogenesis
2) Hormone-dependent involution of tissues in the adult. e.g., endometrium
3) Cell loss in proliferating cell populations such as epithelial cells in intestinal crypts
4) Death of host cells after serving their useful purpose. e.g., neutrophils in an acute
inflammatory response
Pathologic
1) DNA damage with radiation, cytotoxic drugs & hypoxia
2) Accumulation of misfolded proteins causing ER stress. e.g., Degenerative diseases of CNS
3) Cell death with viral infections, such as HIV or adenovirus
4) Pathologic atrophy of pancreas or parotid gland after duct obstruction.
Mechanisms Phases: Initiation phase & execution phase
A) Initiation phase: Activation of enzymes, caspases occur in two distinct pathways.
1) Intrinsic (mitochondrial) pathway: Major pathway

Activation of sensors of cellular stress & damage (BAD, BIM, BID), cause antagonism of
anti-apoptotic molecules (BCL-2) & activation of pro-apoptotic molecules (BAX, BAK).
This results in increased permeability of outer membrane of mitochondria leading to release
of cytochrome c into cytoplasm causing activation of initiator caspases (Caspase-9).
2) Extrinsic (death-receptor initiated) pathway: Cross-linking of plasma membrane death
receptors, Type 1 TNF receptor & Fas by external ligands such as TNF & Fas ligand (FasL)
respectively, result in activation of initiator caspases (caspases-8 &-10).
B) Execution phase: Initiator caspases trigger activation of executioner caspases (caspase-3
&-6), which cause disruption of cytoskeleton & fragmentation of nucleus.
Morphology
1) Cell is smaller with dense cytoplasm & tightly packed organelles.
2) Peripheral aggregation of chromatin under the nuclear membrane into dense masses.
3) Nucleus breaks into two or more fragments
3) Surface blebbing, followed by fragmentation into membrane –bound apoptotic bodies.
4) Plasma membrane remains intact with altered structure.
5) Phagocytosis of apoptotic cells or cell bodies, by macrophages.
6) No associated inflammatory response.
Necrosis Vs Apoptosis
Feature Necrosis Apoptosis
Cell size Enlarged Reduced
Nucleus Pyknosis, karyorrhexis, karyolysis Undergo fragmentation
Plasma membrane Disrupted Intact
Cellular contents Enzymatic digestion Intact
Inflammation Frequent Absent
Nature Pathologic Physiologic or pathologic
Autophagy
“It is an adaptive response that is enhanced during nutrient deprivation, allowing the cell to
cannibalize itself to survive.”
Significance:
1) Maintain the integrity of cells by recycling essential metabolites and clearing cellular
debris under various stress conditions.
2) Turnover of organelles like ER, mitochondria, & lysosomes and the clearance of
intracellular aggregates that accumulate during aging & stress.
Mechanisms: 1) Formation of an isolation membrane (phagophore) and its nucleation
2) Elongation of the vesicle
3) Maturation of the autophagosome
4) Fusion with lysosome, and eventual degradation of the contents
Associations: Physiologic – Aging and exercise
Pathologic – Cancer; Alzheimer disease; Inflammatory bowel disease; Infectious diseases
(Mycobacteria, Shigella spp., & HSV-1)
Steatosis (Fatty Change)

Def.: Abnormal accumulation of triglycerides (TGs) within parenchymal cells.
Sites: Liver (MC), heart, muscle & kidney.
Causes: Alcohol abuse, nonalcoholic fatty liver disease, CCl4, protein malnutrition, diabetes
mellitus, obesity, starvation & anoxia.
Fatty liver
Mechanisms: Excessive entry or defective metabolism & export of lipids.

Morphology: Gross Enlarged, bright yellow, soft, greasy organ
Micro. Initially, small clear cytoplasmic vacuoles are seen around the nucleus. Later, they
coalesce, creating large vacuoles, displacing the nucleus to the periphery of the cell.
Heart
Patterns of fatty change

1) Prolonged moderate hypoxia: Gross Apparent bands of yellowed myocardium with
bands of darker, red-brown, uninvolved myocardium –Tigered effect.
Micro. Intracellular deposits of fat in the form of small droplets in the involved myocardium.
2) More profound hypoxia: Gross More uniformly yellowish appearing myocardium.
Micro. Intracellular deposits of fat in the form of small droplets
Special stains for fat: Sudan IV; Sudan III; Sudan black; Oil Red-O
Lipofuscin (Lipochrome or Wear-tear-pigment)

Insoluble endogenous pigment, not injurious to the cell or its functions.
Mechanism: Free radical injury & lipid peroxidation.
Composition: Polymers of lipids & phospholipids in complex with protein.
Morphology: Yellow-brown, finely granular cytoplasmic, often perinuclear pigment.
Associations: Liver & heart of aging patients or patients with severe malnutrition & cancer
cachexia.
Pathologic Calcification
“Abnormal tissue deposition of calcium salts, together with smaller amounts of other mineral
salts.”
Types:
I) Dystrophic calcification
i) Deposition of calcium salts occur locally in dying tissues
ii) Calcium levels & calcium metabolism are normal.
e.g.,: Areas of necrosis (Coagulative, liquefactive or caseous); Aging or damaged heart
valves; Atherosclertotic plques.
Comp.: Organ dysfunction.
II) Metastatic calcification:

i) Deposition of calcium salts in normal tissues
ii) Hypercalcemia is seen with derangements in calcium metabolism.
Causes of hypercalcemia: Hyperparathyroidism; Vit. D intoxication; Renal failure; Multiple
myeloma; Diffuse skeletal metastases.
Sites: MC-Interstitial tissues of the gastric mucosa, kidneys, lungs, systemic arteries &
pulmonary veins.
Comp.: Respiratory compromise; Renal damage.
Morphology: Gross Fine white granules or clumps

Micro. Calcium salts can be intracellular and/or extracellular. They appear basophilic,
amorphous granular or clumped. Psammoma bodies, lamellated concentric calcifications seen
with dystrophic calcification with papillary carcinoma of thyroid or meningioma.
2. Inflammation and Repair
4 Marks
1) Role of complement in inflammation. (July, 2017)

2) Role of prostaglandins in acute inflammation. (Feb. 2017)
3) Phagocytosis. (July, 2015)
4) Mention arachidonic acid metabolites and their role in inflammation. (Jan. 2014)
5) Granuloma. (Jan. 2013)
7) Healing by second intention and complications of wound healing. (July, 2013)
8) Protein derived mediators of acute inflammation. (Jan. 2013)
10) Role of selectins and integrins involved in the inflammatory response. (Jan. 2012)
11) Chemotaxis. (July, 2011)
12) Growth factors involved in tissue regeneration and repair. (Jan. 2011)
13) Arachidonic acid metabolites and their role in inflammation. (Jan. 2011)
14) Chemokines. (March, 2010)
15) Discuss various processes that participate in the formation of a scar. (March, 2010)
16) Healing by first intention. (Aug. 2009)
17) Phagocytosis. (Feb. 2009)
18) Chemotaxis. (Oct. 2008)
19) Giant cells. (March/April, 2008)
20) Cell derived chemical mediators of inflammation. (Sep/Oct. 2007)
21) Healing by second intention. (May, 2007)
22) Fracture healing. (March/April, 2005)
23) Vascular events of inflammation. (Oct. 2005)
24) Factors influencing wound healing. (Oct. 2004)
25) Phagocytosis. (April/May, 2004)
26) Giant cells. (March/April, 2003)
27) Healing of a bone fracture. (March/April, 2003)
2 Marks
1) Give four important causes of granulomatous inflammation. (Feb. 2017)

2) Wound healing by first intention. (July, 2015)
3) Fibrinous inflammation. (Jan. 2015)
4) Name four (4) causes of granuloma formation. (July/Aug. 2014)
5) Name any four (4) growth factors involved in regeneration and wound healing. (Jan. 2014)
6) Name 4 main components of extra cellular matrix (ECM). (Jan. 2013)
7) Name four chemical mediators of inflammation. (Aug. 2010)
8) Various types of giant cells. (Aug. 2009)
9) Granuloma. (April, 2009)
10) Cardinal signs of acute inflammation. (April, 2009)
11) Healing by second intension. (Oct. 2008)
12) Complications of wound healing. (Sept/Oct. 2007)
13) Triple response. (May, 2007)
14) Giant cells. (May, 2006)
15) Chemotaxis. (May, 2006)
16) Granuloma. (March/April, 2005)
17) Granuloma. (Sep. 2003)
18) Healing of a wound by second intention. (Sep. 2003)
Cardinal Signs of Inflammation

RuboràRedness
CaloràHeat
TumoràSwelling
DoloràPain
Functio laesaàLoss of function
Vascular Events of Acute Inflammation

I) Arteriolar vasodilation
Stimulus: Histamine
Effects: 1) Increased volume of blood in flow generates heat (calor).
2) Increased supply of oxygenated blood makes tissues turn red (rubor or erythema)
3) Increased hydrostatic pressure
II) Increased vascular permeability
Mechanisms:
1) Contraction of endothelial cells with increased interendothelial space (MC):
Stimulus: Histamine (Major), bradykinin, leukotrienes
Features: Immediate transient response; Reversible; Venules are most commonly involved
2) Endothelial injury causing necrosis & their detachment:
Stimulus: Severe injury (Burns), Microbes
Features: Immediate sustained response; Irreversible; Arterioles, capillaries & venules are
involved.
Effects: 1) Escape of protein rich fluid into interstitial tissues causing edema (Tumor).
2) Decreased plasma oncotic pressure
3) Increased viscosity with concentration of blood cells.
4) Slow or no flow of blood (stasis), disrupts normal laminar flow.
Triple Response
Demonstrated by Lewis experiment with the changes in the skin of inner aspect of forearm by
firm stroking with a blunt point.
Features:
1) Red line: Appears within seconds due to local dilation of capillaries & venules
2) Flare: Bright reddish appearance surrounding red line with arteriolar vasodilation
3) Wheal: Swelling of surrounding skin due to edema
Complementary Adhesion Molecules

Two major families of molecules are the selectins & integrins, and their ligands.
Site: Expressed on leukocytes & endothelium.
Stimulus: Cytokines
Function: Mediate rolling, adhesion & transmigration
I) Selectins: P-selectin, E-selectin & L-selectin

Site: P-selectin & E-selectin are expressed on endothelium; L-selectin on leukocytes.
Ligands: Selectins bind to sialylated oligosaccharides bound to glycoproteins.
Interactions:
P-selectin (endothelium) – Sialyl-Lewis X (leukocytes)
E-selectin (endothelium) – Sialyl-Lewis X (leukocytes)
L-selectin (leukocytes) - Sialyl-Lewis X (Endothelium)
Function: Mediate rolling
II) Integrins: ICAM-1, VCAM-1 & PECAM-1

A) ICAM-1, VCAM-1
Site: Endothelium
Ligands: Immunoglobulin family molecules (LFA-1, Mac-1, VLA-4)
Interactions:
ICAM-1 (endothelium) – LFA-1 & Mac-1 (leukocytes)
VCAM-1 (endothelium) – VLA-4 (leukocytes)
Function: Mediate adhesion
B) PECAM-1
Site: Leukocytes & endothelium
Function: Mediate transmigration with homotypic interactions.
Chemotaxis
“Locomotion along a chemical gradient within tissues toward the site of injury mediated by
chemoattractants.”
Chemoattractants:
1) Exogenous: Bacterial products (peptides or lipids)
2) Endogenous: Mediators (Leukotriene B4; C5a; Chemokines)
Mechanisms: Chemoattractants bind to specific 7-transmembrane G protein-coupled
receptors on the surface of the leukocytes, causing polymerization of actin. Leukocytes move
by extending pseudopods that bind the ECM & then pull the cell forward.
Phagocytosis
Steps
I) Recognition & attachment: Mediated by mannose receptors, scavenger receptors &
receptors for opsonins expressed on phagocytes.
II) Engulfment: Polymerization of actin filaments facilitate pseudopods formation with
engulfed material in phagosome. Phagosome fuses with lysosomes forming phagolysosome
into which discharge of granules content occur.
III) Killing & degradation: Done by ROS, reactive nitrogen species & lysosomal contents.
1) ROS are produced in the presence of NADPH oxidase enzyme. Myeloperoxidase mediates
formation of hypochlorite from hydrogen peroxide in the presence of chloride. Hypochlorite
destroys microbes by halogenation or oxidation of proteins & lipids.
2) Reactive nitrogen species are produced in the presence of nitric oxide synthase enzyme.
Reaction of nitric oxide with superoxide anion forms peroxynitrite.
3) ROS & peroxynitrite damage proteins, lipids & nucleic acid of microbes
4) Lysosomal contents such as acid proteases, elastases, defensins, lysozyme, lactoferrin &
major basic protein are involved in degradation of microbes.
Fibrinous Inflammation
“A morphologic pattern of acute inflammation.”
Mechanism: With marked raise in vascular permeability, fibrinogen may escape and get
converted to fibrin in ECS, forming fibrinous exudate.
e.g., Meningitis, pericarditis, pleuritis
Microscopy: Eosinophilic meshwork of threads
Outcome: Dissolution or organization
Mediators of Inflammation
Cell-derived mediators: Vasoactive amines; Arachidonic acid metabolite; Cytokines;

PAF
Plasm-derive mediators: Complement proteins; Bradykinin
I) Vasoactive amines
“Histamine & serotonin, preformed mediators, are the first to be released during
inflammation.”
Histamine
Stimulus: Physical injury; Immediate hypersensitivity reactions; anaphylatoxins

Source: Mast cells (Major); Basophils & platelets
Function: Arteriolar vasodilation & increased vascular permeability of venules
II) Arachidonic acid metabolites (Eicosanoids)
“Leukotrienes (LTs) & prostaglandins (PGs) are formed from arachidonic acid present in
membrane phospholipids.”
Stimulus: Mechanical, chemical & physical stimuli.
I) Prostaglandins: Cyclooxygenase enzyme yields prostaglandins like PG E2, PG D2, PG
F2a, Thromboxane (TXA2), and prostacyclin (PGI2)
Source: Macrophages, mast cells & endothelial cells.
Functions:
Thromboxane A2: Aggregation of platelets & vasoconstriction
Prostacyclin: Inhibition of platelet aggregation & vasodilation
PG E2, PG D2: Vasodilation and increased vascular permeability
PGF2a: Contraction of smooth muscle & small arterioles
PG E2: Pain and fever
II) Leukotrienes: Lipoxygenase enzyme yields leukotrienes such as: LTB4, LTC4, LTD4,
LTE4
Source: Leukocytes & mast cells
Functions: LTB4: Chemotaxis
LTC4, LTD4 & LTE4: Vasoconstriction, bronchospasm & increased vascular permeability
III) Lipoxins: Lipoxygenase enzyme yields lipoxins such as Lipoxin A4 (LXA4) & Lipoxin
B4 (LXB4)
Function: Suppress inflammation by inhibiting the recruitment of leukocytes.
III) Cytokines
“They are essentially tumor Necrosis Factor (TNF) & Interleukin-1 (IL-1).”
Source: Macrophages & dendritic cells
Stimulus: Microbial products, immune complexes & physical injury
Functions:
1) Both TNF & IL-1 cause endothelial activation (increased expression of adhesion
molecules, production of various mediators & increased procoagulant activity) and induce
systemic acute-phase response (fever).
2) TNF activates leukocytes & IL-1 activates fibroblasts to synthesize collagen
3) TNF regulates energy balance by promoting lipid & protein mobilization and by
suppressing appetite.
IV) Chemokines
Stimulus: Microbial products

Groups:
I) C-X-C chemokines: e.g., IL-8
Function: Activation & chemotaxis of neutrophils
II) C-C chemokines: e.g., Eotaxin, MCP-1, RANTES, MIP-1
Function: Chemotaxis of eosinophils, basophils, lymphocytes, & monocytes.
III) C chemokines: e.g., Lymphotactin
Function: Chemotaxis of lymphocytes
IV) CX3C chemokines: e.g., Fractalkine
Function: Chemotaxis of monocytes and T lymphocytes
Functions:
I) Inflammatory chemokines: Facilitate adhesion & chemotaxis of leukocytes
II) Homeostatic chemokines: Organize various cell types in different anatomic regions of
the tissues.
V) Platelet –Activating Factor (PAF)
Source: Platelets, mast cells, neutrophils, macrophages & endothelial cells

Function: Platelet aggregation, vasoconstriction & bronchoconstriction.
VI) Complement system
“Soluble plasma proteins seen in inactive forms, numbered C1 through C9.”

Complement activation: It involves formation of proteolytic enzymes, C3 convertase & C5
convertase by 3 pathways.
1) Classical pathway, triggered by fixation of C1 to antibody combined with antigen.
2) Alternative pathway, triggered by microbial products (endotoxin) & cobra venom
3) Lectin pathway, where plasma mannose-binding lectin binds to carbohydrates on
microbes & directly activates C1.
End products:
1) C3 convertase splits C3 into C3a & C3b
2) C5 convertase splits C5 into C5a & C5b
3) Membrane Attack Complex is formed by binding of C5b with C6, C7, C8 & C9.
Functions
1) C3a & C5a act as anaphylatoxins, stimulate the release of histamine from mast cells &
cause vasodilation and increased vascular permeability.
2) C5a facilitates chemotaxis & activates the lipoxygenase pathways of AA metabolism
3) C3b acts as opsonin & facilitates phagocytosis of microbes.
4) MAC deposition cause cell death.
VII) Bradykinin
Source: Derived from high-molecular-weight kininogen by the action of enzyme, kallikrein.

Function: Increased vascular permeability, vasodilation, contraction of smooth muscle &
pain.
Granulomatous Inflammation
“A form of chronic inflammation characterized by the formation of granulomas.”
Causes: TB; Leprosy; Syphilis; Cat-scratch disease; Sarcoidosis; Crohn disease
Features
I) Epithelioid cells: Activated macrophages with pink granular cytoplasm & indistinct cell
boundaries resembling epithelial cells.
II) Giant cells: Many activated macrophages fuse forming multinucleated giant cells with
abundant cytoplasm & many nuclei
Types: 1) Foreign-body type: Nuclei are seen arranged in a haphazard pattern
2) Langhans type: Nuclei are seen arranged in a particular pattern
III) Granuloma: Focal collections of epithelioid cells with giant cells surrounded by a rim of
lymphocytes.
Types: 1) Immune granuloma: i) Associated with persistent microbes in the presence of T-
cell mediated immune responses.
ii) Macrophages activate T cells to produce cytokines, such as IL-12, which activates other T
cells & IFN-gamma, which activates macrophages.
2) Foreign body granuloma: i) Seen with relatively inert foreign bodies (talc; sutures) in the
absence of T-cell mediated immune responses.
ii) Foreign material is usually identified in the centre of granuloma with epithelioid cells &
giant cells apposed to its surface.
IV) Caseous necrosis: Granulomas with central caseous necrosis are known as caseating
granulomas, seen with TB. Non-caseating granulomas are seen with sarcoidosis, Crohn
disease.
Growth Factors Involved in Regeneration and Repair

Growth factors stimulate the activity of genes that are required for cell growth & cell
division.
1) Epidermal growth factor (EGF)
Source: Macrophages, keratinocytes
Function: Mitogenic for keratinocytes & fibroblasts
2) Vascular Endothelial Growth Factor (VEGF)
Source: Mesenchymal cells
Stimulus: Hypoxia
Function: Angiogenesis by promoting endothelial cell migration & proliferation.
Vasodilation & increased vascular permeability.
3) Platelet-Derived Growth Factor (PDGF)
Source: Platelets, macrophages, endothelial cells, smooth muscle cells
Function: Proliferation of fibroblasts, endothelial cells & smooth muscle cells. Chemotactic
for neutrophils, macrophages, fibroblasts & smooth muscle cells
4) Fibroblast Growth Factor (FGF)
Source: Macrophages, mast cells, endothelial cells.
Function: Chemotactic & mitogenic for fibroblasts. Stimulates angiogenesis & ECM protein
synthesis
5) Transforming Growth Factor-beta (TGF-beta)
Source: Platelets, endothelial cells & mononuclear inflammatory cells
Function: Stimulates ECM synthesis & prevents break down of collagen causing scar
formation. Limits & terminates inflammatory response as an anti-inflammatory cytokine.
Healing of Skin Wounds

“It involves both epithelial regeneration & the formation of connective tissue scar.”
Types
Healing by First Intension or Primary Union
1) Seen with minimal injury to skin, where edges of the wound are approximate.
2) Healing is by regeneration.
3) It involves small clot formation, minimal necrotic debris, mild inflammatory response,
minimal granulation tissue deposition & insignificant scar.
4) Wound contraction is not seen.
E.g., Healing of a clean, uninfected surgical incision approximated by sutures.
Healing by Second Intention or Secondary Union

1) Seen with extensive damage to skin, where edges of the wound are distant.
2) Healing is by regeneration & fibrosis.
3) It involves larger clot formation, greater necrotic debris, more intense inflammatory
response, abundant granulation tissue deposition & significant scar formation.
4) Wound contraction is seen.
E.g., Large wounds, abscesses, ulceration & infarction of parenchymal organs
Steps
1) Coagulation pathway activation results in formation of a clot covering wound surface.

With dehydration, clot transforms to a scab.
2) Within 24 hrs. neutrophils are recruited involved in clearing of debris.
3) Within 24 to 48 hrs, epithelial cells from both edges of the wound have begun to migrate
and proliferate along the dermis, depositing basement membrane under the scab. Finally, a
thin continuous epithelial layer closes the wound
4) By day 3, macrophages replace neutrophils, & clear the debris & fibrin. Deposition
granulation tissue and collagen follows.
5) By day 5, granulation tissue fills the tissue deficit with prominent neovascularization.
Fibroblast migration and proliferation is seen with deposition of abundant collagen.
Epidermis recovers its normal thickness.
6) During the second week, increasing collagen deposition & the regression of vascular
channels begins with diminished inflammatory response.
7) By the end of first month, formed scar comprises of a cellular connective tissue largely
devoid of inflammatory cells & covered by an essentially normal epidermis.
8) Wound contraction: In secondary union, formation of a network of myofibroblasts seen at
the edge of the wound. Their contraction helps to close the wound by decreasing the gap
between its dermal edges & by reducing the surface area of wound.
Healing of Fractures
“Fracture healing involves reactivating bone formation pathways, regulated by cytokines and
growth factors.”
Events:
I) During the first week
1) Hematoma forms immediately after fracture, filling the fracture gap
2) Clot provides a fibrin meshwork for the influx of inflammatory cells and ingrowth of
fibroblasts and new capillaries
3) Growth factors (PDGF, TGF-g & FGF) activate osteoprogenitor cells and stimulate
osteoclastic and osteoblastic activity
4) Finally, fusiform, predominantly uncalcified tissue called, soft tissue callus or procallus is
formed providing anchorage between the ends of fractured bones.
II) Within 2 weeks
1) Activated osteoprogenitor cells deposit subperiosteal trabeculae of woven bone
2) Activated mesenchymal cells differentiate into chondrocytes that make cartilage which
undergoes enchondral ossification
3) Finally, soft tissue callus is transformed into a bony callus which stabilizes the fracture
site.
4) Bony callus is eventually remodeled along lines of weight bearing and the healing process
is complete with lamellar bone having medullary cavity.
Factors that influence healing: Inadequate immobilization, malalignment, infection of the
fracture site, malnutrition and skeletal dysplasia
Complications: Delayed union or nonunion; Pseudoarthrosis
Factors That Influence Tissue Repair

They can be extrinsic or intrinsic to the injured tissue and systemic or local.
1) Infection: Delays healing

2) Diabetes: Delays healing
3) Nutritional factors such as protein deficiency & Vit.C deficiency: Retards healing
4) Glucocorticoids: Diminish fibrosis & cause weakness of scar
5) Mechanical factors such as increased local pressure: Cause wound dehiscence
6) Poor perfusion with arteriosclerosis or diabetes: Impairs healing
8) Foreign bodies such as fragments of steel or glass: Impairs healing
9) Type of tissue: Labile & stable tissues have better tissue regeneration, whereas permanent
tissues form only scar.
Complications in Tissue Repair

I) Wound dehiscence & ulceration
Mechanisms: Inadequate formation of granulation tissue or formation of a scar.
E.g., Abdominal wounds with vomiting or coughing may undergo dehiscence or rupture;
Atherosclerotic peripheral vascular disease causes wound of lower limb ulcerate.
II) Hypertrophic scar & keloids
Mechanisms: Accumulation of excessive amounts of collagen
Morphology: Hypertrophic scar is a raised scar lying within boundaries of original wound,
but in keloids, scar tissue grows beyond the boundaries & does not regress.
E.g., Thermal or traumatic injuries may cause hypertrophic scar
Keloids are MC in African Americans
III) Exuberant granulation
Mechanism: Formation of excessive amounts of granulation tissue
Morphology: Seen as a protrusion above the level of surrounding skin
E.g., Following incisional scar or traumatic injuries (rare).
IV) Contractures
Mechanism: Exaggeration of wound contraction
E.g., Severe burns cause contractures involving palms, soles & anterior aspect of the thorax.
Comp.: Deformities of wound & surrounding tissues.
3. Hemodynamic Disorders, Thromboembolic

Disease, and Shock
10 Marks
1) A 55 year old lady was brought to the emergency room unconscious. Her blood pressure
was very low, pulse was weak and rapid. Her skin was warm and flushed. Her blood culture
revealed growth of Gram positive bacteria. (Jan. 2015)
a) What is the possible diagnosis?

b) Describe the pathogenesis of this condition.
c) Describe the stages of this disorder.
Ans: Septic shock
2) Young male met with an accident. Had fracture femur. C/o breathlessness and chest pain,
cough and frothy sputum. (Jan. 2013)
a) What is the provisional diagnosis?

b) What other conditions can produce similar symptoms?
Ans: Fat embolism
4 Marks
1) Pathogenesis of septic shock. (July, 2017)

2) Systemic thromboembolism. (July, 2016)
3) Air embolism. (July, 2015)
4) Pathogenesis of endotoxic shock. (July/Aug. 2014)
5) Etiology and pathogenesis of fat embolism. (Jan. 2014)
6) Systemic thromboembolism. (Jan. 2012)
7) Exudate and transudate. (April, 2009)
8) Thromboembolism. (April, 2009)
9) Fate of thrombus. (Feb. 2009)
10) Thromboembolism. (March/April, 2008)
11) Cardiac edema. (May, 2007)
12) Septic shock. (May, 2006)
13) C.V.C. Liver. (Oct. 2005)
14) Nephrotic edema. (March/April, 2005)
15) Amniotic fluid embolism. (Sep. 2003)
2 Marks
1) Fate of thrombus. (Feb. 2017)

2) Fate of thrombus. (July, 2013)
3) Nutmeg liver. (July, 2012)
4) Fate of a thrombus. (July, 2011)
5) Hypovolemic shock. (July, 2011)
6) Phlebothrombosis. (Jan. 2011)
7) Fate of a thrombus. (Aug. 2010)
8) What is paradoxical embolism? Give an example. (March, 2010)
9) Mural thrombus. (Aug. 2009)
10) Exudate and transudate. (April, 2009)
11) Thromboembolism. (April, 2009)
12) Exudate. (Feb. 2009)
13) Cardiac edema. (Oct. 2008)
14) Shock lung. (March/April, 2008)
15) Stages of shock. (Sept/Oct. 2007)
16) Fate of a thrombus. (May, 2006)
17) Amniotic fluid embolism. (May, 2006)
18) Fate of thrombus. (Oct. 2005)
19) Air embolism. (March/April, 2005)
20) Paradoxical embolism. (April/May, 2004)
21) Nutmeg liver. (April/May, 2004)
22) Brown induration of the lung. (Sep. 2003)
23) Decompensated shock. (March/April, 2003)
Cardiac Edema
Causes: Congestive cardiac failure
Pathogenesis: Increased capillary hydrostatic pressure and retention of sodium & water with
activated renin-angiotensin system causes development of edema.
Type of edema: Transudate
Renal Edema
Causes: Nephrotic syndrome; Renal failure
Pathogenesis:
1) Nephrotic syndrome: Decreased plasma osmotic pressure with massive proteinuria and
retention of sodium & water with activated renin-angiotensin system leads to edema.
2) Renal failure: Retention of sodium and water with activated renin-angiotensin system
causes increased hydrostatic pressure and decreased plasma osmotic pressure leading to
edema
Type of edema: Transudate
Transudate Vs Exudate
Feature Transudate Exudate
Cause Increased hydrostatic pressure Increased vascular permeability
or decreased oncotic pressure
Nature Non-inflammatory Inflammatory
Appearance Clear Cloudy
Protein Low (<3 gm/dl) High (>3gm/dl)
Specific gravity <1.012 >1.020
Cellularity Poor Rich
Fibrin Absent Present
Pitting Present Absent
Chronic Passive Hepatic Congestion

Def.: Increased blood volumes within liver due to impaired outflow for prolonged duration.
Cause: Congestive heart failure
Pathogenesis: 1) Chronic hypoxia leads to ischemic injury of tissues.
2) Capillary rupture causes hemorrhage and formation of hemosiderin-laden macrophages
Morphology: Gross Nutmeg liver: Centrilobular regions are red-brown & slightly depressed
and are accentuated against the surrounding zones of uncongested tan liver.
Micro. Centrilobular hemorrhage, hemosiderin-laden macrophages, and variable degrees of
hepatocyte dropout and necrosis.
Chronic Passive Pulmonary Congestion

Def.: Increased blood volumes within lung due to impaired outflow for prolonged duration.
Cause: Congestive heart failure
Pathogenesis: 1) Chronic hypoxia leads to ischemic injury of tissues.
2) Capillary rupture causes hemorrhage and formation of hemosiderin-laden macrophages
Morphology: Gross Lungs are firm and heavy. C/S: Rusty brown (brown induration of
lungs)
Micro. Septa are thickened and fibrotic. Numerous hemosiderin-laden macrophages (heart
failure cells) are seen within the alveoli.
Venous Thrombosis (Phlebothrombosis)

Synonyms: Red thrombi or stasis thrombi
Pathogenesis: Formed with stasis or hypercoagulability in the sluggish venous circulation
Site: Veins of lower extremity (MC)
Morphology: Firm solid masses, focally attached to the vessel wall and contain lines of
Zahn. They appear red with more RBCs and relatively few platelets, forming a long luminal
cast and extend in the direction of blood flow.
C/P: Always occlusive causing ischemia.
Fate: Propagation; Embolization; Dissolution; Organization or recanalization
Mural Thrombus
Def.: Thrombi seen in heart chambers or in the aortic lumen.
Pathogenesis: Formed with endothelial injury or turbulence
Causes: Myocardial infarction, dilated cardiomyopathy, myocarditis, arrhythmias,
atherosclerosis, aneurysms.
Morphology: Firm solid masses, focally attached to the vessel wall and contain lines of
Zahn.
They consist of a friable meshwork of platelets, fibrin, red cells, and degenerating leukocytes.
C/P: May be occlusive causing ischemia
Fate: Propagation; Embolization; Dissolution; Organization or recanalization
Fate of Thrombus
Over a period of time, thrombi are seen undergoing any of the following changes.
1) Propagation: Thrombi accumulate additional platelets and fibrin
2) Embolization: Thrombi dislodge and travel to other sites in the vasculature
3) Dissolution: Thrombi may shrink and disappear with fibrinolysis
4) Organization & Recanalization: Thrombi may organize with ingrowth of endothelial
cells, smooth muscle cells, and fibroblasts. Recanalization is seen with formation of capillary
lumens.
Thromboembolism
MC type of embolism
Def.: Emboli are dislodged thrombi, carried by the blood from its point of origin to a distant
site.
Types
I) Systemic thromboembolism
Def.: Emboli in the arterial circulation

Origin: Intracardiac mural thrombi
Causes: Left ventricular wall infarcts (MC), aortic aneurysms, atherosclerotic plaques,
vegetations or paradoxical emboli.
Sites of lodgement: Lower extremities (MC); Brain; Kidneys; Intestines
C/P: Ischemia causing infarction
II) Pulmonary embolism
"MC form of thromboembolic disease.”

Mostly, pulmonary emboli are multiple and small.
Origin: Deep veins of lower limb (DVTs)
Sites of lodgement: Main pulmonary artery, bifurcation of pulmonary artery, or smaller,
branching arteries.
C/P: 1) Asymptomatic (MC): Seen with small emboli being organized with time.
2) Sudden death, right heart failure or cardiovascular collapse: Seen with emboli
obstructing 60% or more of pulmonary circulation.
3) Hemorrhage: Seen with embolic obstruction of medium-sized arteries with subsequent
vascular rupture.
4) Hemorrhage or infarction: Seen with embolic obstruction of small end-arteriolar
pulmonary branches.
5) Pulmonary hypertension & right ventricular failure: Seen with multiple emboli over
time.
Paradoxical Embolism
Def.: Emboli originating in venous circulation, but gain access to the systemic arterial
circulation with interatrial or interventricular defects.
Association: ASD; VSD
C/P: Result in systemic thromboembolism
Fat and Marrow Embolism

Causes: Fractures of long bones (MC), soft tissue trauma and burns
Pathogenesis: 1) Rupture of vascular sinusoids in the marrow or small venules will allow
marrow or adipose tissue into the vasculature.
2) Fat microemboli & associated red cell and platelet aggregates can occlude the pulmonary
& cerebral microvasculature.
3) Release of FFA from fat globules cause toxic injury to endothelium
C/P: 1-3 days after injury sudden onset of tachypnea, dyspnea, & tachycardia; irritability &
restlessness progressing to delirium or coma are seen. A diffuse petechial rash may be seen.
Fat Embolism Syndrome – Anemia, thrombocytopenia, pulmonary insufficiency and
neurologic symptoms
Diagnosis: Microscopic demonstration of fat globules in pulmonary vasculature with frozen
section and special stains for fat.
Amniotic Fluid Embolism

Cause: Occurs as a complication of labor & the immediate postpartum period
Pathogenesis: 1) Tear in the placental membranes or rupture of uterine veins allow infusion
of amniotic fluid or fetal tissue into maternal circulation.
2) Substances in amniotic fluid activate coagulation factors causing DIC.
Morphology: Maternal lungs show edema, diffuse alveolar damage & the presence of fibrin
thrombi in many vascular beds.
C/P: Sudden onset of severe dyspnea; cyanosis & shock; neurologic impairment as headache,
seizures & coma are seen.
Diagnosis: Microscopic demonstration of fetal squamous cells, lanugo hair, fat & mucins in
the maternal pulmonary circulation.
Comp.: Maternal death or permanent neurological deficit
Air Embolism
Causes: Obstetric or laparoscopic procedures, chest wall injury, or decompression sickness
Decompression sickness
Predisposing factors: Deep sea diving or underwater construction

Pathogenesis: 1) Exposure to sudden decreases in atmospheric pressure causes the nitrogen
comes out of solution in the tissues and the blood.
2) Rapid formation of gas bubbles seen within skeletal muscles and supporting tissues in &
about joints and pulmonary vasculature causing ischemic injury.
Morphology: Lungs show edema, hemorrhage, and focal atelectasis or emphysema
Pathogenesis: Nitrogen gas embolism
C/P: 1) Bends: Painful musculoskeletal condition
2) Chokes: A form of respiratory distress
Caisson disease
“Chronic form of decompression sickness.”

Pathogenesis: Persistence of gas emboli in the skeletal system leads to ischemic necrosis
involving bones.
Sites affected: Head of femur, tibia & humerus
Shock
Def.: Shock is a state in which diminished cardiac output or reduced effective circulating
blood volume impairs tissue perfusion and leads to cellular hypoxia.
Types: 1) Cardiogenic shock 2) Hypovolemic shock 3) Shock associated with systemic
inflammation 4) Neurogenic shock 5) Anaphylactic shock
Hypovolemic shock
Causes: Massive hemorrhage or fluid loss from vomiting, diarrhea or severe burns
Pathogenesis: Low blood volume causes low cardiac output leading to tissue ischemia.
Septic shock
“MC cause of death in ICU.”

Causes: Gram +ve bacteria (MC), gram -ve bacteria and fungi
Pathogenesis: Microbial products mediate various events.
1) Activation of inflammatory cells (neutrophils & monocytes) with production of cytokines
(IL-1, TNF) mediate endothelial activation and systemic effects such as fever, diminished
myocardial contractility and metabolic abnormalities.
2) Activation of complement cascade mediate endothelial activation
3) Endothelial activation results in production of various mediators (IL-6, IL-8, NO & PAF)
leading to vasodilation, increased permeability and tissue hypoperfusion
4) Activation of coagulation cascade along with endothelial activation induces a procoagulant
state causes DIC leading to tissue ischemia
5) Finally, multiorgan failure is seen.
Stages of shock
I) Nonprogressive phase:
1) Reflex compensatory mechanisms are activated. (e.g., Baroreceptor reflexes,
catecholamine release, ADH release, renin-angiotensin activation and generalized
sympathetic stimulation)
2) Cardiac output and BP are maintained causing tachycardia, peripheral vasoconstriction,
and renal conservation of fluid
II) Progressive phase:
1) Persistent hypoxia results in anaerobic glycolysis with excessive production of lactic acid.
2) Lactic acidosis blunts the vasomotor response causing arteriolar vasodilation
3) Pooling of blood in microcirculation worsens cardiac output & causes endothelial damage
III) Irreversible phase:
1) Irreversible cell injury with lysosomal enzyme leakage, further aggravating the shock state
2) Survival is not possible even if the hemodynamic defects are corrected.
Morphology: Brain: Ischemic encephalopathy with liquefactive necrosis;
Heart: Coagulative necrosis; Adrenals: Cortical lipid cell depletion;
Kidneys: Acute tubular necrosis (ATN)
Lungs: Shock lung (Cause: Sepsis or trauma. Morphology: Diffuse alveolar damage)
C/P: 1) Hypotension; a weak, rapid pulse; tachypnea; and cool, clammy cyanotic skin.
2) Decreased urine output and DIC in later stages.
4. Genetic Disorders
4 Marks
1) Klinefelter syndrome. (Feb. 2017)

2) Name four autosomal dominant diseases. (Jan. 2016)
3) Klinefelter syndrome. (July, 2015)
5) Down syndrome. (Jan. 2013)
6) Turner syndrome. (July, 2012)
8) Klinefelter syndrome. (Aug. 2009)
9) Turners syndrome. (April, 2009)
10) Klinefelter syndrome. (Sept/Oct. 2007)
11) Klinefelter syndrome. (April/May, 2004)
12) Down syndrome. (Sep. 2003)
2 Marks
1) Name four clinical features of trisomy 21. (July, 2016)

2) Name four autosomal dominant diseases. (Jan. 2016)
3) Name four (4) clinical features of Turner Syndrome. (July/Aug 2014)
4) Name three (3) X-linked recessive and one (1) X-linked dominant disorders. (Jan. 2014)
5) Barr bodies. (Jan. 2012)
6) Clinical features and karyotypes of Turner Syndrome. (Jan. 2011)
7) Name two cytogenetic disorders involving sex chromosomes and two involving
autosomes. (March, 2010)
8) Down syndrome. (Oct. 2008)
9) Barr body. (March/April, 2008)
10) Down syndrome. (Oct. 2005)
11) Turner syndrome. (March/April, 2005)
12) Turner syndrome. (March/April, 2003)
Autosomal Dominant Disorders

Familial hypercholesterolemia; Marfan syndrome; Hereditary spherocytosis;
Neurofibromatosis; Adult polycystic kidney disease
X-Linked Recessive Disorders

Hemophilia A & B; G6PD deficiency; Duchenne muscular dystrophy; Wiskott-Aldrich
syndrome; Fragile X syndrome
X-Linked Dominant Disorders

Vitamin D-resistant rickets
Cytogenetic Disorders Involving Autosomes

Trisomy 21 (Down syndrome); Trisomy 18 (Edward syndrome); Trisomy 13 (Patau
syndrome)
Cytogenetic Disorders Involving Sex Chromosomes

Turner syndrome; Klinefelter syndrome
Barr Body (X chromatin)

Lyon hypothesis: 1) Only one of the X chromosomes is genetically active. The other X
undergoes heteropyknosis & is rendered inactive.
2) Inactivation of X occurs at random among all the cells of blastocyst on or about day 5.5 of
embryonic life.
3) The inactive X, seen as a darkly staining small mass in contact with the nuclear membrane
in the interphase nucleus is knows as Barr body.
Detection of Barr body: Buccal smear
Turner Syndrome
“MC sex chromosome abnormality in females.”
Genetic alteration: Partial or complete monosomy of the X chromosome.
Pathogenesis: Absence of 2nd X chromosome causes loss of oocytes leading to
hypogonadism.
Karyotypes: 1) Classic: 45, X
2) Defective 2nd X chromosome: An isochromosome of the long arm (46,X,i(Xq))
3) Mosaic type: 45,X/46XX
C/P: 1) During infancy: Edema of the dorsum of hand & foot; Swelling of nape of neck
causing cystic hygroma; Bilateral neck webbing is seen later.
Associations: Congenital heart disease (Pre-ductal coarctation of aorta & bicuspid aortic
valve)
2) Adolescence & adults: Failure to develop normal secondary sex characteristics during
puberty (Infantile genitalia, inadequate breast development & little pubic hair); Shortness of
stature; Cubitus valgus; Broad chest & widely placed nipples; Primary amenorrhea;
Infertility; Ovaries reduced to atrophic fibrous strands (streak ovaries).
Associations: Hypothyroidism; Glucose intolerance, obesity & insulin resistance.
Klinefelter Syndrome
“Male hypogonadism that occurs when there are 2 or more X chromosomes & one or more Y
chromosomes.”
Karyotype: 47XXY (MC)
Risk factor: Increased maternal age
Genetic alteration: Nondisjunction during the meiotic divisions in the germ cells of one of
the parents. Reduced spermatogenesis leads to hypogonadism.
Morphology (Testis): Gross Small atrophic testes.
Miro. Seminiferous tubules may appear atrophic, replaced by collagenous ghosts or
embryonic, consisting of cords of cells. Leydig cells appear prominent.
C/P: Elongated appearance with an increase in length between the soles & the pubic bone;
Eunuchoid body habitus with abnormally long legs; Small testes; Small penis; Lack of
secondary sex characteristics as deep voice & beard; Gynecomastia; Infertility
Associations: Type 2 diabetes & metabolic syndrome; Mitral valve prolapse; Osteoporosis &
fractures; Breast cancer; SLE; Extragonadal germ cell tumors.
Inv.: Elevated plasma gonadotropin (FSH) levels; Reduced testosterone levels; Elevated
mean plasma estradiol levels.
Trisomy 21 (Down Syndrome)

“MC chromosomal disorder.”
Karyotype: 47 XX +21(MC); Robertsonian translocation (Rare)
Risk factor: Increased maternal age
Genetic alteration: Meiotic nondisjunction of chr. 21 in ovum
C/P: Flat facial profile, oblique palpebral fissures, & epicanthic folds; Severe mental
retardation; Gap between 1st & 2nd toe; Hypotonia; Simian crease; Abundant neck skin.
Associations: Congenital heart disease (endocardial cushion defects-ASD, VSD); Acute
leukemias (ALL & AML); Alzheimer disease; Severe infections.
Diagnostic tests during pregnancy: Chorionic villus sampling and amniocentesis
5. Diseases of the Immune System
10 Marks
1) A 60 year old patient long history of rheumatoid arthritis presented with enlarged tongue
and a history of diarrhea. Urine shows positive heat test for proteins and ECG shows
conduction disturbances. (July/Aug. 2014)
a) What is the possible diagnosis and what will be ideal site for biopsy to confirm it?
b) Name the lab technique for definite diagnosis.
c) Write four (4) types of this abnormal substance and their associated diseases.
d) Give the structural details of the substance.
Ans: Amyloidosis
2) A homosexual individual who is also an intravenous drug abuser with history of persistent
generalized lymphadenopathy (PGL) and chronic diarrhea came to sexually transmitted
diseases (STD) OPD with mucosal candidiasis, fever, oral hairy leukoplakia and loss of more
than 10% body weight. There is a fall in CD4+T cell count. (Jan. 2011)

b) Describe the sequences of events in the pathogenesis of the disease.
c) Discuss various tests used for diagnosis and for monitoring treatment of the same.
Ans: AIDS
4 Marks
1) Pathogenesis of type I hypersensitivity reaction. (July, 2015)

2) Type IV hypersensitivity reaction. (Jan. 2015)
3) Describe the chemical nature of Amyloid. (Jan. 2014)
4) Pathogenesis of amyloidosis. (Jan. 2013)
5) Antinuclear antibodies. (July, 2012)
6) Physical and chemical nature of amyloid. (Jan. 2012)
7) Amyloidosis of spleen. (July, 2011)
8) CNS manifestations of AIDS. (Aug. 2010)
9) Pathogenesis of amyloidosis. (March, 2010)
10) Nature of amyloid. (March/April, 2008)
2 Marks
1) Mention four examples of antibody mediated type-II hypersensitivity reaction. (July, 2017)
2) Four special stains for demonstration of amyloid. (Feb. 2017)
3) Give four examples of type II hypersensitivity. (July, 2016)
4) Give four (4) examples of type I hypersensitivity reaction. (July/Aug. 2014)
5) Sago spleen. (July, 2013)
6) Bence-Jones Protein. (Jan. 2013)
7) Sago spleen (Aug. 2009)
8) Lardaceous spleen. (April, 2009)
9) Special stains used in amyloidosis. (Feb. 2009)
10) L.E cell. (Oct. 2008)
11) Antinuclear antibody. (May, 2007)
12) Amyloid spleen. (Oct. 2005)
13) Amyloid spleen. (April/May, 2004)
Immediate (Type I) Hypersensitivity

“It is a rapid immunological reaction occurring in a previously sensitized individual.”
Pathogenesis:
i) Presentation of the antigen (allergen) to naïve CD4+ helper T cells induce differentiation of
T cells into TH2 cells.
ii) Exaggerated TH2 response is seen with secretion of cytokines (IL-4, IL-5, IL-13) that
promote inflammation & stimulate IgE production from B cells.
iii) IgE binds to the Fc receptors on submucosal mast cells, and repeat exposure to allergen
trigger the mast cells to release granule contents & produce various mediators.
iv) Early-phase reaction: Occurs within min. after exposure to an allergen with vasodilation,
increased vascular permeability, bronchoconstriction, and increased mucus production are
seen.
Mediators & effects:
a) Leukotrienes C4, D4 & E4: Bronchoconstriction, increased vascular permeability &
increased mucus secretion.
b) Cytokines (IL-1, TNF & chemokines): Promote leukocyte recruitment
c) Histamine: Increased vascular permeability and smooth muscle contraction
c) Prostaglandin D2: Bronchoconstriction & vasodilation
d) Platelet-activating factor: Platelet aggregation
v) Late-phase reaction: Occurs 2 to 24 hrs later with recruitment of eosinophils, neutrophils
& T lymphocytes with tissue damage. Eosinophils liberate proteolytic enzymes and proteins
(major basic protein & eosinophil cationic protein) which damage tissues.
Associations: Hay fever, Bronchial asthma; Allergic gastroenteritis; Anaphylaxis
Antibody-Mediated (Type II) Hypersensitivity

“Antibodies mediate disease upon reaction with antigens present on cell surfaces or in ECM.”
Pathogenesis:
1) Opsonization of cells by antibodies and complement compounds and ingestion by
phagocytes
2) Inflammation induced by antibody binding to Fc receptor of leukocytes and by
complement breakdown products
3) Antireceptor antibodies disturb the normal function of receptors
Associations: Autoimmune hemolytic anemia; Goodpasture syndrome; Myasthenia gravis;
Pemphigus vulgaris; Graves disease; Acute rheumatic fever; Pernicious anemia
T Cell-Mediated (Type IV) Hypersensitivity

“CD4+ T cells and CD8+ T cells are involved.”
I) CD4+ T Cell-Mediated inflammation
CD4+ T cells secrete cytokines, which mediate chronic inflammation and tissue damage.
Pathogenesis:
i) Naïve CD4+ T cells recognize peptides displayed by antigen presenting cells (APCs) and
secrete IL-2, which stimulate proliferation of the antigen responsive T cells.
ii) APCs produce IL-12, which induces differentiation of CD+ T cells to TH1 subset and IL-
23, which induces differentiation of CD+ T cells to TH17 subset.
iii) Upon repeat exposure to an antigen, TH1 cells secrete IFN-g, which mediates macrophage
activation to facilitate elimination of offending antigen. Granulomatous inflammation and
tissue damage may follow.
iv) Activated TH17 cells secrete IL-17, IL-22 and chemokines, which recruit neutrophils and
monocytes.
Associations: Delayed-type hypersensitivity (DTH); Tuberculin reaction; Contact dermatitis;
Drug reactions; Rheumatic arthritis; Multiple sclerosis
II) CD8+ T Cell-Mediated Cytotoxicity

CD8+ cytotoxic T lymphocytes (CTLs) mediate killing of antigen-expressing target cells and
tissue destruction.
Pathogenesis:
1) Activated CTLs express Fas ligand, which can bind to Fas expressed on target cells and
trigger apoptosis.
2) CTLs secrete preformed mediators, perforins and granzymes into the target cells which
trigger apoptosis.
Associations: Type 1 diabetes; Graft rejection; Viral infections; Tumors
Antinuclear antibodies (ANAs)

“These are the antibodies directed against nuclear antigens.”
Significance: 1) Aid in diagnosis and management of various systemic autoimmune diseases
2) Play a role in the pathogenesis of their associated diseases
Associated disorders: SLE (Antibodies to double-stranded DNA & Smith (Sm) antigen are
diagnostic), Systemic sclerosis, Sjogren syndrome
Categories:
1) Antibodies to DNA
2) Antibodies to histone
3) Antibodies to nonhistone proteins bound to RNA
4) Antibodies to nucleolar antigens
Detection methods: Indirect immunofluorescence; ELISA
LE cell (Lupus Erythematosus Cell)

Def.: Any phagocytic cell (neutrophil or macrophage) that has engulfed the denatured
nucleus of an injured cell.
Association: Systemic lupus erythematosus (SLE)
Pathogenesis: In tissues, nuclei of damaged cells react with ANAs, lose their chromatin
pattern, and become homogenous forming LE bodies or hematoxylin bodies. Engulfment of
these denatured nuclei by phagocytic cells form LE cells.
Location: Blood, pericardial or pleural effusions
Detection methods: LE cell demonstration on buffy coat smears; Cytology of body fluids
Amyloidosis
“Amyloidosis represents a group of disorders having in common, deposition of similar
appearing proteins.”
Properties of amyloid
a) General: Pathological proteinaceous substance which is amorphous, eosinophilic and
hyaline
deposited extracellularly.
b) Physical nature: Electron microscopy reveals continuous, nonbranching fibrils. X-ray
crystallography and infrared spectroscopy demonstrate a characteristic cross-b-pleated sheet
conformation.
c) Chemical nature: Fibril proteins (95%)
Types of amyloid
I) Most common forms
1) AL (amyloid light chain): Mostly composed of l Ig light chains or their fragments derived
from plasma cells.
2) AA (amyloid-associated): Derived from SAA (serum amyloid-associated) protein that is
synthesized in the liver.
3) Ab (b-amyloid protein): Derived from amyloid precursor protein.
II) Less common forms
1) TTR (transthyretin): Normal or mutants forms are seen as amyloid deposits.
2) b2-microglobulin: Deposited as amyloid fibril subunit (Ab2m)
3) Prion proteins: Misfolded prion proteins seen as amyloid deposits.
Pathogenesis:
1) Failure of mechanisms involved in clearing of misfolded proteins play the central role.
2) Insoluble misfolded proteins aggregate and deposit as fibrils in extracellular tissues.
3) Categories of protein:
a) Normal proteins that have an inherent tendency to fold improperly, associate and form
fibrils, when they are produced in excessive amounts.
b) Mutant proteins tend to get misfolded and then aggregate.
Classification
A) Systemic (generalized) amyloidosis
I) Primary amyloidosis (Immunocyte dyscrasias with amyloidosis): MC type
Type of amyloid: AL
Associated disorder: Multiple myeloma
Pathogenesis: Malignant plasma cells secrete abnormal amounts of monoclonal Ig and free,
unpaired light chains (Bence-Jones protein). Bence-Jones proteins are seen in serum, excreted
in urine and deposited in tissues as amyloid.
II) Reactive systemic amyloidosis (Secondary amyloidosis)
Type of amyloid: AA
Associated disorders: Rheumatoid arthritis (MC), ankylosing spondylitis, inflammatory
bowel disease, heroin abuse, renal cell carcinoma and Hodgkin lymphoma
B) Localized amyloidosis
Amyloid deposits are limited to a single organ or tissue without involvement of any other site
in the body. E.g., lungs, larynx, skin, urinary bladder or tongue.
Other types
1) Hemodialysis-associated amyloidosis
Associated disease: Chronic renal failure with hemodialysis
Type of amyloid: Ab2m
2) Endocrine amyloid
Associated diseases: Medullary carcinoma of thyroid and type 2 diabetes mellitus
3) Amyloid of aging
Senile systemic amyloidosis (Senile cardiac amyloidosis): Systemic deposition of amyloid in
elderly patients is seen with heart being predominantly involved.
Type of amyloid: TTR (normal)
4) Heredofamilial amyloidosis
a) Familial Mediterranean fever (MC): Autosomal recessive
Type of amyloid: AA
b) Familial amyloidotic neuropathies: Autosomal dominant
Type of amyloid: TTR (mutant)
Morphology
Spleen
Gross: Normal in size or moderate to marked enlargement. Tapioca-like granules are evident
in sago spleen.
Micro.:
1) Sago spleen: Amyloid deposits are largely limited to the splenic follicles
2) Lardaceous spleen: Amyloid deposits in the walls of the splenic sinuses and connective
tissue framework in the red pulp. Fusion of the early deposits gives rise to large, maplike
areas.
C/P: 1) Asymptomatic
2) Non-specific: Weakness, weight loss, light-headedness, or syncope.
3) Specific: Kidney: Nephrotic syndrome; Renal failure and uremia
Heart: Congestive heart failure; Arrhythmias; Restrictive cardiomyopathy
GIT: Malabsorption; Diarrhea
Blood vessels: Bleeding
Diagnosis: 1) Biopsy from kidney or rectal or gingival tissues or abdominal fat aspirates
stained with special stains for amyloid.
Stains for amyloid: Congo red, Crystal violet, Sirius Red, Thioflavin T
2) Serum and urine protein electrophoresis & immunoelectrophoresis
3) Bone marrow aspiration
4) Scintigraphy with radiolabeled serum amyloid P (SAP) component
AIDS
“AIDS is a disease characterized by profound immunosuppression with opportunistic
infections, secondary neoplasms, and neurologic manifestations.”
Cause: HIV (HIV-1 & HIV-2)
Major target systems: Immune system & CNS
Major cellular targets: CD4+ T lymphocytes, macrophages and dendritic cells
Major routes of transmission: Sexual transmission, parenteral transmission, and mother -to-
infant transmission
Pathogenesis:
I) Immune system:
Cell mediated immunity is primarily affected with infection of CD4+ T lymphocytes by
binding of the gp120 envelop glycoprotein to CD4 molecules.
a) Mechanisms of loss of CD4+ T lymphocytes
i) Increased plasma membrane permeability
ii) Virus replication interfering with protein synthesis
iii) Apoptosis & pyroptosis
iv) Loss of immature precursors
v) Fusion followed by death
b) Qualitative defects of CD4+ T lymphocytes: They include a reduction in antigen-induced
T-cell proliferation and defects in intracellular signaling.
II) CNS: Macrophages & microglia are infected. Neurologic deficit is believed to be
indirectly caused by viral products and by soluble factors (IL-1, TNF & IL-6) produced by
infected microglia.
Manifestations:
1) Acute retroviral syndrome: Occurs 3-6 wks after infection
C/P: Sore throat, myalgias, fever, weight loss and fatigue. Diarrhea, vomiting or cervical
adenopathy may occur.
2) Chronic phase (clinical latency period): It may last from 7-10 yrs
C/P: Asymptomatic or develop infections such as candidiasis or herpes zoster
3) Acquired immunodeficiency syndrome (AIDS):
C/P: i) Long-lasting fever, fatigue, weight loss, diarrhea & generalized lymphadenopathy
ii) Opportunistic infections: Viral (JC virus, HSV, CMV & HZV); Bacterial (Salmonella,
Nocardiosis, & Mycobacteriosis); Fungal (Candidiasis, Cryptococcosis, & Histoplasmosis);
Protozoal & Helminthic (Taxoplasmosis, Pneumocystosis, & Cryptosporidiosis)
iii) Secondary neoplasms: Kaposi sarcoma (MC), cervical carcinoma, anal carcinoma in
males and B-cell lymphomas
iv) CNS: Meningoencephalitis, aseptic meningitis, peripheral neuropathies, and HIV-
associated neurocognitive disorder.
Diagnosis:
1) Raised HIV-1 RNA levels in the blood
2) Low CD4+ T lymphocyte counts
3) Antibody tests: ELISA & Western blot
6. Neoplasia
4 Marks
1) Tabulate the differences between lymphatic and vascular spread of tumors. (July, 2017)
2) Differences between benign and malignant tumors. (July, 2016)
3) Tabulate differences between benign and malignant tumors. (Jan. 2016)
4) Enumerate the chemical carcinogens. Give pathogenesis of chemical carcinogenesis. (Jan.
2016)
5) Tumor markers. (July, 2015)
6) Describe the steps / events involved in mechanism of tumor invasion and metastasis. (Jan.
2014)
7) Physical carcinogenesis. (Jan. 2013)
8) Differences between benign and malignant tumors. (July, 2012)
9) Important growth factors modulating tumor growth and biology. (Jan. 2012)
10) Paraneoplastic syndromes. (Jan. 2011)
11) Microbial carcinogenesis. (March, 2010)
12) Chemical carcinogens. (August, 2009)
13) Differences between benign and malignant tumors. (April, 2009)
14) Viral carcinogens. (February, 2009)
15) Tumor markers. (March/April, 2008)
16) Spread of malignant tumors. (Oct. 2008)
17) Chemical carcinogenesis. (Sept/Oct. 2007)
18) Paraneoplastic Syndromes. (May, 2007)
19) Metastasis. (May, 2006)
20) Differences between benign and malignant tumors. (March/April, 2005)
21) Viral oncogenesis. (Sep. 2003)
22) Metastasis. (March/April, 2003)
23) Differences between benign and malignant tumors. (March/April, 2003)
2 Marks
1) Name four tumors caused by various viruses. (Feb. 2017)

2) Name four inherited cancer syndromes. (July, 2016)
3) Name four malignant tumors causing paraneoplastic syndromes. (Jan. 2015)
4) Describe four (4) modes of tumor spread with examples. (July/Aug. 2014)
5) Name one (1) infectious disease and three (3) tumors caused by Epstein-Barr virus
(Jan. 2014)
6) Characteristics of malignant cell. (July, 2013)
7) Pathways of spread of malignant Tumors. (July, 2011)
8) Name four tumor suppressor genes. (Jan. 2011)
9) Grading and staging of cancer. (Sept/Oct. 2007)
10) Anaplasia. (May, 2007)
11) Dysplasia. (March/April, 2005)
12) Spontaneous regression of malignant tumors. (April/May, 2004)
13) Carcinoma-in-situ. (Sep. 2003)
Dysplasia
“It can be considered as a precancerous lesion.”
Site: Usually seen with epithelia.
Predisposing conditions: Metaplasia
Morphology
1) Pleomorphism: Epithelial cells vary in their shape & size.
2) Nucleus: Large & hyperchromatic with increased nuclear-to-cytoplasmic ratio
3) Mitoses: Mitotic rate is high & mitoses involve all levels of epithelium
4) Loss of polarity: Disordered architecture of the tissue is seen.
Fate: Regression or progression to cancer.
Carcinoma In Situ
“It is the preinvasive stage of cancer.”
Morphology: In situ epithelial cancers display marked dysplastic changes involving the full
thickness of the epithelium without invasion of the basement membrane.
Association: Carcinomas of the skin, breast and cervix.
Fate: May progress to invasive carcinoma
Anaplasia
“Anaplasia means lack of differentiation, which is a hallmark of malignant tumors.”
Morphology
1) Pleomorphism: Tumor cells vary in their shape & size. Tumor giant cells with few large
hyperchromatic nuclei with abundant cytoplasm.
2) Abnormal nuclear morphology: Increased nuclear-to-cytoplasm ratio is seen with enlarged
nuclei. Nuclei vary in shape & may appear hyperchromatic. Abnormally large nucleoli may
be seen.
3) Mitoses: Atypical, bizarre mitotic figures and high mitotic rates are seen
4) Loss of polarity: Sheets or large masses of tumor cells grow in an anarchic, disorganized
fashion.
5) Necrosis: Rapidly growing tumors may develop large central areas of ischemic necrosis
Metastasis
Def.: Spread of a tumor to sites that are physically discontinuous with the primary tumor.
It is the most characteristic feature of malignant tumors.
Pathways of spread:
1) Seeding of body cavities & surfaces: Body cavities such as peritoneal (MC), pleural or
pericardial cavity are involved. Seen with ovarian cancers.
2) Lymphatic spread: Spread through lymphatics is seen with carcinomas e.g., carcinoma of
breast & carcinoma of lung. The first node in a regional lymphatic basin that receives lymph
flow from the primary tumor is known as sentinel lymph node.
3) Hematogenous spread: Spread with vascular invasion is seen with sarcomas e.g.,
angiosarcoma, fibrosarcoma. Veins are invaded readily. Some carcinomas like renal cell
carcinoma & hepatocellular carcinoma show hematogenous spread.
Steps of invasion and metastasis

I) Invasion of the extracellular matrix
1) Dissociation of cancer cells from one another with loss of E-cadherin function facilitates
their advance into the surrounding tissues.
2) Proteases (MMPs) secreted by tumor cells or stromal cells cause degradation of the
basement membrane and interstitial connective tissue and release ECM-sequestered growth
factors.
3) Cleavage of the ECM proteins generates novel sites that bind to receptors on tumor cells
and stimulate migration.
4) Tumor cell-derived cytokines facilitate migration of tumor cells through the degraded
basement membranes and zones of matrix proteolysis by contraction of actin cytoskeleton.
II) Vascular dissemination & homing of tumor cells
1) Within the circulation, tumor cells form clumps or emboli.
2) Arrest and extravasation of tumor emboli at distant sites involves adhesion to the
endothelium and egress through the basement membrane.
3) Many tumors arrest in the first capillary bed they encounter (Lung & liver) and some
tumors show organ tropism.
Benign Tumors Vs Malignant Tumors

Feature Benign Malignant
Presentation Circumscribed mass Usually an irregular mass
Differentiation Well differentiated Well differentiated to poorly differentiated
Anaplasia Not seen Can be seen
Rate of growth Slow Usually rapid
Mitotic figures Less and normal Numerous and can be abnormal
Capsule Present Usually absent
Local invasion Usually absent Present
Metastasis Absent Frequently present
Prognosis Good Usually poor
Inherited Cancer Syndromes

Autosomal Dominant
1) Retinoblastoma
2) Li-Fraumeni syndrome
3) MEN syndromes
4) Hereditary nonpolyposis colon cancer (HNPCC)
5) Familial adenomatous polyposis
Autosomal Recessive
1) Ataxia-telangiectasia
2) Bloom syndrome
3) Xeroderma pigmentosum
Tumor Suppressor Genes

In health: They suppress unwanted cell proliferation
In neoplasia: Their loss of function results in unregulated cell growth & genetic instability
leading to tumor formation.
E.g.,
Tumor suppressor gene Associated disorder
APC Colonic carcinoma
RB Retinoblastoma & osteosarcoma
TP53 Li-Fraumeni syndrome
WT1 Wilms tumor
BRCA1 & BRCA2 Carcinoma of breast
Chemical Carcinogenesis
“It is a multistep process involved in mediating development of cancers.”
Steps
I) Initiation: 1) Exposure of cells to a sufficient dose of a carcinogenic agent results in
permanent damage to DNA.
2) Initiation is rapid & irreversible.
3) Alone is not sufficient for tumor formation.
Types of carcinogens
i) Direct acting carcinogens: No requirement of metabolic conversion to become
carcinogenic.
e.g., Alkylating agents; Acylating agents
ii) Indirect acting carcinogens: They require metabolic conversion to become active
carcinogens
e.g., Benzopyrene; Benzidine; 2-Naphthylamine; Aflatoxin B1
II) Promotion: 1) Involves proliferation of initiated cell in the presence of promotors.
2) Promotors can’t induce tumor formation applied before initiation.
3) It is reversible.
Promotors e.g., Phorbol esters, phenols, hormones & drugs
Radiation Carcinogenesis
I) Ultraviolet Rays
UVB light is considered to be carcinogenic.
Pathogenesis: Formation of pyrimidine dimers in DNA
Associated disorders
1) Skin cancers: Basal cell carcinoma, squamous cell carcinoma & melanoma
2) Xeroderma pigmentosum
II) Ionizing Radiation

Source: X-rays, g rays, a particles, b particles, protons, and neutrons
Pathogenesis: 1) Chromosomal breakage
2) Translocations
3) Point mutations
Associated tumors
1) Leukemias (myeloid)
2) Thyroid cancer
3) Cancers of breast, lung & salivary glands
Microbial Carcinogenesis
I) Viruses & associated tumors
1) Human T-Cell Leukemia Virus Type 1 (HTLV 1): Adult T-cell leukemia/lymphoma
2) Human Papilloma Virus (HPV)
Benign tumors: Squamous papilloma
Malignant tumors: Squamous cell carcinomas of the cervix, anogenital region & head, and
neck.
3) Epstein-Barr Virus (EBV)
Burkitt lymphoma; Hodgkin lymphoma; Nasopharyngeal carcinoma; B-cell lymphomas in
immunosuppressed individuals.
4) Hepatitis B & C Viruses (HBV & HCV): Hepatocellular carcinoma
II) Bacteria & associated tumors
Helicobacter pylori: Gastric adenocarcinoma & gastric lymphoma
Paraneoplastic Syndromes
Def.: Symptom complexes that cannot readily be explained by the spread of the tumor.
Significance: 1) Aid in detection of tumors
2) May mimic metastasis
3) Affect prognosis
E.g.,
Endocrinopathies
1) Cushing syndrome Small-cell carcinoma of lung
2) SIADH Small-cell carcinoma of lung
3) Hypercalcemia Squamous cell carcinoma of lung; Breast carcinoma
4) Polycythemia Renal carcinoma
Others
1) Acanthosis nigricans Gastric carcinoma
2) Myasthenia Carcinoma of lung
3) Hypertrophic osteoarthropathy Carcinoma of lung
4) Venous thrombosis Pancreatic carcinoma
5) DIC Acute promyelocytic leukemia
Grading and Staging of Tumors

“Grading and staging gives information about the aggressiveness of tumors and their extent
& spread in individual patients.”
Significance: 1) To determine the treatment protocols
2) To predict the prognosis of tumor
Grading: It is based on the degree of differentiation and no. of mitoses or architecture of the
tumor. Range from 2 to 4 categories.
Staging: It is based on the size of primary tumor, its extent of spread to regional lymph
nodes, and the presence or absence of blood-borne metastases.
TNM system
1) T for primary tumor: T0 for in situ lesion & T1 to T4 on the basis of size of tumor.
2) N for regional lymph node involvement: N0 for no LN involvement. N1 to N3 on the basis
of no. & range of LNs involved.
3) M for metastases: M0 for no distant metastases. M1 or M2 indicates the presence of distant
metastases.
Tumor Markers
“They are tumor-associated enzymes, proteins or hormones detected in the blood.”
Significance: 1) Aid in the detection of tumors
2) To determine the effectiveness of therapy
3) To know the appearance of a tumor recurrence
E.g.,
Hormones
1) HCG Choriocarcinoma
2) Calcitonin Medullary carcinoma of thyroid
3) Catecholamines Pheochromocytoma
Oncofetal antigens
1) Alpha-fetoprotein Hepatocellular carcinoma
2) CEA Carcinomas of the colon, pancreas & lung
Specific proteins
Immunoglobulins Multiple myeloma
PSA Prostate cancer
Mucins
CA-125 Ovarian cancer
CA-19-9 Pancreatic cancer
7. Infectious Diseases
10 Marks
1) A 52 year old beggar is admitted with skin patches and nodules on the face. Skin patches
are hypoesthetic. Few toes on both feet are amputated partly. (July, 2017)
a) What is the possible diagnosis? How will you make the diagnosis?
b) Classify the disease.
c) What special stains will you do on the biopsy to make the diagnosis?
d) Discuss the mode of transmission of the disease.
Ans: Leprosy
4 Marks
1) Give the clinical picture and microscopic picture of the lesion in lepromatous leprosy.
(Jan. 2016)
2) Ghon complex. (Jan. 2015)
3) Morphology of lepromatous leprosy. (July, 2012)
4) Primary complex. (July, 2011)
5) Rhinosporidiosis. (July, 2011)
6) Actinomycosis. (Aug. 2010)
7) Primary complex. (Aug. 2009)
8) Lepromatous leprosy. (Oct. 2008)
9) Primary complex. (May, 2006)
10) Actinomycosis. (Oct. 2005)
11) Opportunistic fungal infection. (March/April, 2005)
12) Tuberculoid leprosy. (April/May, 2004)
13) Lepromatous leprosy. (March/April, 2003)
2 Marks
1) Tuberculoid leprosy – Microscopic picture. (July, 2013)

2) Mention 4 sequelae of Ghon complex. (Jan. 2013)
3) Late manifestations of congenital syphilis. (Jan. 2012)
4) Miliary tuberculosis (Aug. 2010)
5) Morphology of actinomycotic mycetoma. (March, 2010)
6) Rhinosporidiosis. (April, 2009)
7) Rhinosporidiosis. (March/April, 2008)
8) Mycetoma. (Sep/Oct. 2007)
9) Lepromatous leprosy. (May, 2007)
10) Mycetoma. (April/May, 2004)
11) Fate of primary tuberculosis. (Sep. 2003)
12) Maduromycosis. (March/April, 2003)
Actinomycosis
“A chronic suppurative disease with systemic illness.”
Causative agent: Actinomycetes israelii (filamentous bacteria)
Sex: M>F
Route of transmission: Endogenous
Types
1) Cervicofacial (MC):
Risk factors: Dental caries, periodontal disease & injury to oral mucosa.
Site: Firm swelling is seen involving lower jaw with abscess & sinus tract formation. May
extend to involve mandible, orbit, cranial bones or CNS
2) Thoracic:
Risk factors: Aspiration of infectious material or extension from abdominal or hepatic
lesions.
Site: Lungs are involved commonly, may extend to pleura & chest wall
3) Abdominal:
Risk factors: Swallowing of infectious material; extension of a thoracic lesion.
Site: Ileocecal region is commonly involved
4) Pelvic:
Risk factors: Usage of IUCD
Morphology: 1) Suppurative & granulomatous inflammation with the formation of

abscesses, containing one or more sulphur granules.
2) Granules are composed of branched, gram +ve filaments, haphazardly arranged in an
amorphous matrix & surrounded by neutrophils and bordered by eosinophilic, club like
material (Splendore –Hoeppli phenomenon).
Inv.: Biopsy, culture & immunofluorescence staining
Mycetoma (Madura Foot or Maduromycosis)

“Mycetoma is a chronic infection of the skin, subcutaneous tissue & sometimes bone
characterized by discharging sinuses filled with organisms.”
Site: Hands or Feet (MC)
Sex: M>F
Age: 20-50yrs
Etiology:
1) Actinomycetoma: Caused by bacteria (Actinomadura madurae; Actinomadura pelletieri;
Nocardia sps.)
2) Eumycetoma: Caused by fungi (Madurella mycetomatis; Madurella grisea)
Pathogenesis: The organism is inoculated into the skin by a minor injury such as a cut with a
thorn when barefoot.
Morphology: Gross 1) Initially, small hard painless lump is seen under the skin which grows
slowly to involve underlying muscle & bone.
2) The middle of the lesion caves in, ulcerates & discharges pus, which contains grains -sinus
formation.
3) Later, surface skin is scarred & pale.
Micro. 1) Localized abscesses are seen involving dermis & subcutaneous tissue with one or
more granules in the centre.
2) Granules of actinomycotic mycetomas contain delicate, gram +ve, branched filaments.
3) Granules of eumycotic mycetomas contain broad, septate, fungal hyphae.
Rhinosporidiosis
Causative organism: Rhinosporidium seeberi (a parasite)
Sex: M>F
Age: Children & 15-40yrs
Site: Mucus membrane of nasopharynx, oropharynx, conjunctiva & rectum
Route of transmission: Contact with contaminated water & autoinfection.
Pathogenesis: After inoculation, the organism replicates locally, causing hyperplasia of the
host tissue & localized immune response.
Morphology: Gross Pink to deep red polyps with strawberry like appearance. Bleeds easily
upon manipulation.
Micro. Surface epithelium exhibits papillomatous hyperplasia. Stroma is hypervascular
showing acute & chronic inflammatory cells with scattered granulomas and sporangia with
endospores.
C/P: Nasal cavity: Unilateral nasal obstruction, epistaxis, rhinorrhea, local pruritus
Eye: Photophobia & increased tearing
Inv.: Biopsy
Syphilis
“A chronic STD”
Causative agent: Treponema pallidum (A Spirochete)
Route of transmission: Sexual & transplacental
Pathogenesis:
1) TH1 response is seen with production of IFN-g which mediates macrophage activation and
killing of bacteria.
2) Production of treponeme-specific antibodies activate complement cascade leading to
opsonization of bacteria by macrophages
3) TprK, a protein in the outer membrane facilitates the persistence of bacteria.
Stages:
I) Primary syphilis: Seen 3weeks after infection.
C/P: 1) Chancre: Single, firm, nontender, raised red lesion which may undergo ulceration
Sites: Penis or scrotum in males; vulva or cervix in females.
2) Regional lymphadenopathy
Morphology: Proliferative endarteritis with rich infiltrate of plasma cells.
II) Secondary syphilis: Seen 2-10 wks after primary chancre
C/P: 1) Red brown macular rash involving palms & soles
2) Silvery-gray superficial erosions on oral or genital mucus membranes
3) Condyloma lata: Broad-based, elevated plaques on inner thigh, anogenital region or axilla
4) Systemic manifestations: Weight loss, mild fever, and lymphadenopathy
Morphology: Proliferative endarteritis with rich infiltrate of plasma cells.
III) Latent syphilis: Symptom free interval

IV) Tertiary syphilis: After a latent period of 5 or more yrs
a) Benign tertiary syphilis:
Gummas are seen as single or multiple, gray-white & rubbery nodular lesions at various sites.
e.g., Bone/joints (pain, swelling or fracture); Skin/Mucus membranes (nodular lesions);
Liver involvement seen with scarring is known as hepar lobatum.
Microscopy: Coagulative necrosis is seen in the center with palisading macrophages &
fibroblasts in the periphery surrounded by plasma cells.
b) Cardiovascular syphilis: MC
Syphilitic aortitis is seen with dilation of the aortic root & arch causing aortic valve
insufficiency and aneurysms of the proximal aorta
c) Neurosyphilis: Asymptomatic or symptomatic
C/P: Meningovascualr syphilis; Tabes dorsalis; General paresis
Congenital syphilis
Cause: Maternal primary or secondary syphilis

Manifestations:
1) Intrauterine death & perinatal death may occur with untreated cases.
2) Infantile syphilis: Manifestations seen during first 2 yrs of life
Snuffles: Nasal discharge and congestion
Rash: Bullous rash of hands & feet and around mouth & anus with epidermal sloughing.
Bone: Osteochondritis & periostitis affects all bones
e.g., Nose – Saddle nose deformity; Tibia – Saber shin
Liver: Diffuse fibrosis with lymphoplasmacytic infiltrate & vascular changes
Lungs: Diffuse Interstitial fibrosis; Pale & airless lungs (pneumonia alba) are seen with
stillborns
2) Tardive syphilis: Manifestations seen during childhood
Triad: Interstitial Keratitis, Hutchinson teeth (small incisors shaped like a peg, often with
notches in the enamel) & 8th nerve deafness
Diagnosis: 1) Biopsy with dark field microscopy & silver stains (Warthin-Starry stain)
2) Immunofluorescence
3) Serological tests:
i) Non treponemal antibody tests: a) Rapid plasma regain (RPR) test
b) Venereal disease research laboratory (VDRL) test
ii) Treponemal antibody tests
a) Fluorescent treponemal antibody absorption test (FTA-Abs)
b) Treponema pallidum enzyme immunoassay test
Leprosy (Hansen Disease)

Causative agent: Mycobacterium leprae (acid fast bacilli)
Route of transmission: Not known. Human respiratory secretions or soil is thought to be
involved.
Ridley-Jopling Classification: Tuberculoid (TT); Borderline Tuberculoid (BT); Borderline
(BB); Borderline Lepromatous (BL); Lepromatous (LL)
Types
I) Tuberculoid (Paucibacillary) leprosy: Less severe form
Sites: Skin and large peripheral nerves

Pathogenesis:
1) TH1 response is seen with production of IFN-g, which causes macrophage activation and
killing of bacteria leading to low bacterial burden
3) Asymmetric neuronal involvement with nerve degeneration causes skin anesthesia with
atrophy of skin and muscle
Morphology: Gross
1) Localized flat, red lesions with indurated, elevated & hyperpigmented margins and pale
depressed center are seen
2) Chronic skin ulcers, contractures, paralysis or amputation of digits seen
3) Eyelid paralysis, keratitis & corneal ulceration are seen with facial nerve involvement
Micro. 1) Granulomatous inflammatory response with less or no bacteria.
2) Grenz zone is absent with inflammatory response encroaching upon the basal layer of
epidermis
II) Lepromatous (Anergic; Multibacillary) leprosy: More severe form
Sites: Skin, peripheral nerves (ulnar & peroneal), testes, hands & feet
Pathogenesis:
1) Weak TH 1 response is seen with lower levels of IL-12 or unresponsiveness of T cell to IL-
12.
2) Some cases show relative increase in TH2 response with production of IL-4, IL-5 & IL-10,
which may suppress macrophage activation
3) Weak cell mediated immunity presents with heavy bacterial burden
4) Widespread invasion of schwann cells, endoneural & perineural macrophages causes
damage to the peripheral nervous system
5) Antibody production mediates immune complex formation causing erythema nodosum,
vasculitis or glomerulonephritis
Morphology: Gross
1) Skin: Hypoesthetic or anesthetic macular, popular or nodular lesions.
2) Leonine facies: Nodular lesions coalesce giving lion-like appearance
Micro: 1) Lepra cells: Large aggregates of lipid-laden macrophages, often filled with masses
(globi) of acid-fast bacilli.
2) Grenz zone: Sub-epidermal uninvolved clear zone separating epidermis from dermis
infiltrated with lepra cells.
Inv.:
1) Biopsy: Stains used - Ziehl-Neelson; Fite-Faraco & GMS (Gomori Methenamine Silver)
2) Lepromin test: Non reactive (negative) in lepromatous leprosy; reactive (positive) in
tuberculoid leprosy.
Tuberculosis
“A chronic pulmonary & systemic disease.”
Causative agent: Mycobacterium tuberculosis (acid-fast bacilli)
Route of transmission: Person to person
Risk factors: Poverty; Crowding; Chronic debilitating illness
Predisposing conditions: Diabetes mellitus; Hodgkin lymphoma; Chronic lung disease
(silicosis); Chronic renal failure; Malnutrition; Alcoholism; Immunosuppression (AIDS).
Pathogenesis:
1) Phagocytosis of microorganisms by macrophages
2) Inhibition of maturation of the phagosome & formation of phagolysosome facilitates
replication of microorganisms in macrophages
3) After 3 wk. of infection, TH1 response is initiated with the release of IL-12
4) TH1-mediated macrophage activation & killing of bacteria seen with production of IFN-g
5) Granulomatous inflammation & tissue damage results finally.
Types
1) Primary tuberculosis
Host: Previously unexposed & unsensitized (non-immune) person

Source: Exogenous
Site: Lungs (Upper lobe - Lower part; Lower lobe – Upper part)
Morphology: Gross
1) Ghon focus: 1-1.5 cm gray-white lesion with cheesy white appearing center.
2) Ghon complex: Gohn focus along with lymphadenopathy.
3) Fibrosis
4) Ranke complex: Radiologically detectable calcification is seen
5) A tiny fibrocalcific pulmonary nodule is seen finally.
Micro. Tubercles (granulomas with central caseous necrosis) are seen
C/P: 1) Asymptomatic (MC)
2) Progressive form: Acute bacterial pneumonia with consolidation of the lobe, hilar
adenopathy & pleural effusion.
3) Lympohematogenous dissemination: Tuberculous meningitis & military TB
Fate: 1) Healed lesion, where organisms are not visible.
2) Latent lesion, where organisms are dormant.
3) Progressive primary TB, which may progress to miliary TB
2) Secondary tuberculosis
Host: Previously sensitized host, many years after primary with weakening of host resistance.
Source: Reactivation of a latent infection or exogenous reinfection
Site: Apex of upper lobes
Morphology:
Gross 1) Small circumscribed firm, gray-white to yellow apical foci with central cheesy-
white appearance are seen
2) Cavitation or erosion into airways is associated
Micro. Tubercles (granulomas with central caseous necrosis) are seen
2) Systemic manifestations: Anorexia, weight loss, fever (mild-grade), night sweats
3) Mucoid or purulent sputum or hemoptysis
4) Pleuritic pain
Fate: 1) Fibrocalcific scars in immunocompetent persons
2) Progressive secondary TB, which may progress to miliary TB
Other forms of TB
A) Progressive pulmonary tuberculosis
Host: Older or immunosuppressed
Morphology:
1) Lung: Apical lesion tends to involve adjacent lung with erosion of bronchi & vessels.
Cavitation is seen through central caseation
2) Pleura: Serous pleural effusions or tuberculous empyema or obliterative fibrous pleuritis
Fate: Fibrosis or miliary tuberculosis
B) Miliary tuberculosis
1) Miliary pulmonary tuberculosis: Microorganisms circulate back to lung via
lymphohematogenous dissemination. Small (2-mm) foci of yellow-white consolidation are
seen scattered through the lung parenchyma.
2) Systemic miliary tuberculosis: Systemic arterial dissemination of bacteria is seen with
involvement of various organs such as liver, spleen, adrenals or meninges.
C) Isolated tuberculosis
Renal tuberculosis; Intestinal tuberculosis; Tuberculous meningitis; Salpingitis;
Osteomyelitis; Tuberculous adrenalitis; Pott disease
Diagnosis
1) History and examination
2) Acid fast stain or culture of the sputum
3) Mantoux or tuberculin skin test
4) PCR
8. Environmental and Nutritional Diseases
4 Marks
1) Morphologic changes in kwashiorkor. (July, 2016)

2) Bone changes in rickets. (July/Aug. 2014)
3) Examples of radiation injury and morphological changes induced by them. (July/Aug. 2014)
4) Ionizing radiation. (Oct. 2005)
2 Marks
1) Mention four effects of radiation. (July, 2017)

2) Four skeletal abnormalities in rickets. (July, 2015)
3) Four alcohol induced diseases. (Jan. 2015)
4) Name any four (4) pathological changes in vitamin A deficiency. (Jan. 2014)
5) Skeletal changes in rickets. (Jan. 2012)
6) Vitamin A deficiency consequences. (Aug. 2010)
7) Consequences of vitamin A deficiency disease. (Aug. 2009)
8) Vitamin C deficiency. (Feb. 2009)
9) Rickets. (Oct. 2008)
10) Lesions of vitamin A deficiency. (March/April, 2008)
11) Vitamin A deficiency disorders. (March/April, 2003)
Effects of Alcohol
I) Acute alcoholism
Liver: Fatty change or hepatic steatosis
Stomach: Acute gastritis and ulceration
CNS: Drowsiness; Stupor and coma with higher alcohol levels.
II) Chronic alcoholism
Liver: Alcoholic hepatitis and cirrhosis with complications such as portal hypertension and
hepatocellular carcinoma
GIT: Massive bleeding from gastritis, gastric ulcer or esophageal varices
Nutrition: Malnutrition and thiamine deficiency with peripheral neuropathies and the
Wernicke-Korsakoff syndrome
CVS: Dilated congestive cardiomyopathy, hypertension and coronary heart disease
Pancreas: Acute and chronic pancreatitis
During pregnancy: Fetal alcohol syndrome with microcephaly, growth retardation, and facial
abnormalities in the newborn.
Cancer: Oral cavity, esophagus, and liver cancers.
Injury Produced by Ionizing Radiation

Source: X-rays, g rays, a particles, b particles, protons, and neutrons
Target tissues: Gonads, bone marrow, lymphoid tissue, mucosa of GIT
Pathogenesis:
1) DNA damage in the form of single-base damage, single- and double-stranded breaks, and
DNA-protein cross links
2) Production of ROS causing DNA damage
3) Endothelial damage causes narrowing or occlusion of blood vessels leading to chronic
ischemic atrophy and fibrosis
Manifestations: May be early or late
Brain: Damage during embryonic development
Skin: Erythema & edema (early); Atrophy & cancer (late)
Lungs: Edema & ARDS (early); Interstitial fibrosis (late)
GIT: Mucosal damage (early); Fibrosis of wall (late)
Lymph nodes: Acute tissue loss (early); Atrophy & fibrosis (late)
Gonads (testes & ovaries): Sterility (early); Atrophy & fibrosis (late)
Blood & Bone marrow: Anemia, granulocytopenia, lymphopenia & thrombocytopenia (early)
Cancers: Leukemias (myeloid); Thyroid cancer; Cancers of breast, lung & salivary glands
Kwashiorkor
“Kwashiorkor is a component of protein energy malnutrition seen with malnourished
children.”
Causes: 1) Protein deprivation, which is relatively greater than the reduction in total calories
2) Chronic diarrhea, nephrotic syndrome or severe burns
Manifestations:
1) Severe loss of the visceral protein compartment with hypoalbuminemia gives rise to edema
2) There is relative sparing of subcutaneous fat and muscle mass
3) Flaky paint appearance of skin with alternating zones of hyperpigmentation, areas of
desquamation, and hypopigmentation
4) Hair changes include overall loss of color or alternating bands of pale & darker hair
5) Development of apathy, listlessness and loss of appetite
6) Vitamin deficiencies, and secondary infections due to immune dysfunction
Morphology: 1) Growth failure with peripheral edema
2) Enlarged fatty liver
3) Small bowel shows mucosal atrophy and loss of villi
4) Thymic and lymphoid atrophy
5) Bone marrow may be hypoplastic
Vitamin A Deficiency
Causes: 1) Decreased intake
2) Malabsorption syndromes
Manifestations:
Eye 1) Night blindness: Impaired vision, particularly in reduced light
2) Xerosis conjunctivae: Dryness of conjunctiva
3) Bitot spots: Keratin debris in small opaque plaques
4) Keratomalacia: Softening & destruction of cornea
5) Total blindness
Skin: Follicular or papular dermatoses
Respiratory tract: Secondary pulmonary infections
Urinary tract: Renal & bladder stones
Immunity: Increased risk of developing infections e.g., measles, pneumonia & infectious
diarrhea.
Vitamin D Deficiency
Causes: 1) Inadequate intake
2) Limited exposure to sunlight
3) Renal disorders
4) Malabsorption syndromes
Deficiency states: Rickets & osteomalacia
Rickets
Vitamin D deficiency in growing children causes rickets.

Age: MC during first year of life
Morphology: 1) Overgrowth of epiphyseal cartilage
2) Persistence of distorted, irregular masses of cartilage
3) Deposition of osteoid matrix on inadequately mineralized cartilaginous remnants
4) Disruption of the orderly replacement of cartilage by osteoid matrix
5) Abnormal overgrowth of capillaries and fibroblasts in the disorganized zone
6) Deformation of the skeleton
Manifestations:
1) Nonambulatory stage of infancy:
i) Flattening of occipital bones
ii) Craniotabes: Parietal bones are soft, & when pressure applied, they will collapse
underneath it
iv) Frontal bossing & a squared appearance of head
v) Rachitic rosary: Expansion of the anterior rib ends at the costochondral junctions
vi) Pigeon breast deformity: Anterior protrusion of sternum
II) Ambulating child: Lumbar lordosis & bowing of the legs
Osteomalacia
Vitamin D deficiency in adults causes Osteomalacia.

Morphology:
1) Derangement of normal bone remodeling
2) Deposition of inadequately mineralized osteoid matrix
3) Weakened bones
C/P: Increased risk of fractures affecting vertebral bodies & femoral necks
Vitamin C Deficiency
“Deficiency of water-soluble vitamin C leads to development of scurvy.”
Causes: 1) Elderly people
2) Chronic alcoholism
3) Erratic & inadequate eating patterns
Manifestations:
1) Growing children: Bone disease with inadequate synthesis of osteoid due to defective
collagen
2) Children & adults: Hemorrhages (bleeding gums, bleeding into skin, periosteum & joints)
and healing defects due to defective collagen
9. Diseases of White Blood Cells, Lymph Nodes,

Spleen, and Thymus
10 Marks
1) A 3 year old child is admitted with fever and petechial hemorrhages for 2 weeks. On
examination child is pale, no liver/spleen enlargement. Cervical lymph nodes are enlarged.
TLC – 50, 000/cumm. Peripheral smear shows blast cells. (Feb. 2017)
a) What is the probable diagnosis?

b) What is the bone marrow picture in this disease?
c) Enumerate the various prognostic factors.
d) Tabulate the differences between lymphoblast and myeloblast.
Ans: Acute Lymphoblastic Leukemia (ALL)
2) A male child aged 8 years presented with fever, fatigue, generalized lymphadenopathy,
bone pain, petechial hemorrhages over the skin, pallor, enlarged testes and features of
meningism. (Jan. 2014)

b) Describe blood and bone marrow picture.
c) Other investigations to confirm the diagnosis.
d) Discuss the prognosis of the same.
3) A 35 year old male was admitted with easy fatigability, anorexia, weakness, weight loss,
night sweats and dragging sensation in the abdomen due to massive splenomegaly. His total
WBC count was 2,00,000 cells/mm3. (July, 2013)

b) Describe the blood and bone marrow picture.
c) Describe the chromosomal abnormality of the disease.
d) Mention various phases of the disease.
Ans: Chronic Myelogenous Leukemia (CML)

4) A 4 years old male child presented with fatigue, fever, epistaxis, bleeding gums, bone pain
and CNS manifestations from meningeal involvement. Physical examination revealed
petechiae and ecchymoses of skin and mucous membranes, generalized lymphadenopathy
and testicular enlargement. The Leukocyte and differential counts were abnormal. (Jan. 2012)

b) Discuss various main laboratory investigations to make a final diagnosis.
c) Describe peripheral blood and bone marrow picture.
d) Discuss molecular pathogenesis of the disease.
5) A 35 year old male patient presented with high fever, fatigue, pallor, skin petechiae,
swollen gums and bone pains. His total WBC count was 1,00,000/ul. (Aug. 2009)

b) Describe the blood and bone marrow picture of the above case.
c) Discuss the prognosis of this disease.
Ans: Acute Myeloid Leukemia (AML)
6) 45 year old male presented with weakness, fatigue, weight loss, night sweats and dragging
sensation in the abdomen caused by massive splenomegaly. (Feb. 2009)

b) What blood investigations should be done to confirm the diagnosis? Describe the
peripheral smear findings.
c) Which chromosomal abnormality is seen in this condition?
7) A 40 year male was admitted with easy fatigability, weakness, weight loss and night
sweats. On examination, massive splenomegaly was noted. Total leukocyte count was 275,
000/ul. (Sep/Oct. 2007)
a) What is the possible diagnosis?
b) Describe the chromosomal abnormality of the disease.
c) Describe the peripheral blood smear and bone marrow findings of the same.
8) A 2 year old child presented with fatigue, fever, epistaxis, bleeding gums and bone pain.
On examination, generalized lymphadenopathy and hepatosplenomegaly was noted. Total
leukocyte count was 150,000/ul. (May, 2007)

b) Describe the cytogenetics of the disease.
c) Describe the peripheral blood smear and bone marrow findings of the same.
d) Describe the prognostic factors of the disease.

9) 36 year old female came with swollen gums, fatigue and weight loss. She gives history of
repeated upper respiratory tract infections. On examination pallor, fever and
hepatosplenomegaly present. (May, 2006)

b) Mention various investigations to make a final diagnosis.
c) Emphasize on the peripheral blood and bone marrow picture.
Ans: Acute Myeloid Leukemia (AML)
10) A 30 years old male patient came with moderate anemia, easy fatigability, weakness,
weight loss, anorexia, dragging sensation in the abdomen due to extreme splenomegaly.
Chromosomal analysis revealed the presence of Philadelphia chromosome. (April/May 2004)

b) Describe the laboratory investigations to make a final diagnosis.
c) Describe the blood and bone marrow picture of the disease.
4 Marks
1) Classify chronic myeloproliferative disorders. Give blood picture and diagnostic tests in a
case of chronic myeloid leukemia. (July, 2017)
2) Leukemoid reaction. (July, 2016)
3) Cytochemistry in differentiation of acute leukemias. (Jan. 2016)
4) FAB classification of Acute Myeloblastic Leukemia (AML). (Jan. 2015)
5) Tabulate the differences between leukemoid reaction and chronic myeloid leukemia.
(July/Aug. 2014)
6) Blood picture and bone marrow findings in CML. (Aug. 2010)
7) Leukemoid reaction. (March/April 2005)
2 Marks
1) Mention four clinical features of acute lymphoblastic leukemia. (July, 2017)

2) Name four subtypes of Hodgkin disease. (July, 2016)
3) Name any four myeloproliferative disorders. (July, 2015)
4) Draw a diagram of Reed-Sternberg cell. (July/Aug. 2014)
5) Mention 4 morphologic characteristics of a myeloblast. (Jan. 2013)
6) Myeloblast of AML 3. (March, 2010)
7) Juvenile chronic myeloid leukemia. (March/April, 2008)
Lymphadenopathy
Causes of generalized lymphadenopathy:
1) Infections: Infectious mononucleosis; Measles; HIV; TB; Syphilis
2) Malignancies: Leukemias; Lymphomas; Metastatic cancers
3) Storage disorders: Niemann-Pick disease; Gaucher disease
4) Autoimmune disorders: SLE; Rheumatoid arthritis
4) Drug reactions: Phenytoin; Allopurinol
Acute Lymphoblastic Leukemia/Lymphoma (ALL)

“MC cancer and leading cause of cancer deaths in children.”
Cell of origin: Precursor B or T cells
Age: <15yrs
Sex: Boys>Girls
Types: B-ALLs (MC) & T-ALLs
Genetic alterations: 1) T- ALLS – Gain of function mutations in NOTCH 1 gene.
2) B-ALLs – Loss of function mutations in PAX5, E2A & EBF genes.
3) Hyperploidy is common
Pathogenesis: Genetic aberrations block the maturation of lymphoid progenitors with their
proliferation & survival.
Diagnosis:
I) Bone marrow: Hypercellular marrow showing many lymphoblasts with interspersed
macrophages gives starry sky appearance.
II) Peripheral smear: 1) Anemia, neutropenia & thrombocytopenia are present.
2) Total leukocyte count is variable with many lymphoblasts.
Lymphoblast: Immature cells with more condensed chromatin, less conspicuous nucleoli,
smaller amounts of cytoplasm with no granules.
III) Cytochemistry: Lymphoblasts are myeloperoxidase negative & PAS positive.
IV) C/P: 1) Fatigue & weakness; Recurrent infections with fever; Bleeding manifestations.
2) Bone pain; Generalized lymphadenopathy, splenomegaly, hepatomegaly, & testicular
enlargement.
3) Headache, vomiting & nerve palsies with CNS involvement.
Prognosis: I) Worse prognosis with 1) Age < 2yrs
2) Presentation in adolescence or adulthood 3) Peripheral blood blast counts >100,000/uL
II) Favorable prognosis with 1) Age between 2 & 10yrs 2) A low white cell count
3) Hyperdiploidy 4) Presence of a t(12;21) 5) Trisomy of chromosomes 4, 7, and 10.
Acute Myeloid Leukemia (AML)

“It is a tumor of hematopoietic progenitors with the accumulation of immature myeloid blasts
in the marrow.”
Cell of origin: Hematopoietic progenitor cells
Age: >60yrs (MC)
Genetic alterations:
1) Balanced chromosomal translocations such as t(8;21), inv(16) & t(15;17) are seen with
AML arising de novo in patients with no risk factors
2) Deletions or monosomies involving chromosomes 5 & 7 are seen with AML that follow
MDS or exposure to DNA-damaging agents.
Pathogenesis: Genetic aberrations block the maturation of myeloid progenitors with their
proliferation & survival.
WHO Classification:
1) AML with genetic aberrations (e.g., t(8;21); inv(16))
2) AML with MDS-like features
3) AML, therapy-related
4) AML, Not Otherwise Specified
AML, minimally differentiated
AML without maturation
AML with myelocytic maturation
AML with myelomonocytic maturation
AML with monocytic maturation
AML with erythroid maturation
AML with megakaryocytic maturation
Diagnosis:
I) Bone marrow: Hypercellular marrow showing many myeloblasts (20% or more -
Diagnostic). Some of the forms of AML are seen having monoblasts.
II) Peripheral smear: 1) Anemia, neutropenia, & thrombocytopenia are present.
2) Total WBC count is variable with many myeloblasts.
3) Aleukemic leukemia: Blasts are entirely absent on peripheral smear.
Myeloblast: Immature cells with delicate nuclear chromatin, 2 to 4 nucleoli, more
voluminous cytoplasm with fine azurophil granules. Auer rods are needle-like azurophil
granules, seen prominently with acute promyelocytic leukemia.
Monoblast: Immature cells with folded or lobulated nuclei. No Auer rods seen.
III) Cytochemistry: 1) Myeloblasts are myeloperoxidase positive & PAS negative
2) Monoblasts are nonspecific esterase (NSE) positive. But, myeloperoxidase negative &
PAS negative.
IV) C/P: 1) Fatigue & weakness; Recurrent infections with fever; Bleeding manifestations.
2) DIC may be seen with acute promyelocytic leukemia.
3) Gingival swelling or skin infiltration (leukemia cutis) may be seen in AML with
monocytic differentiation.
4) Rarely, localized soft tissue mass (myeloblastoma, granulocytic sarcoma or chloroma) may
be seen.
Prognosis: 1) Good for AMLs with the t(15;17).
2) Bad for AMLs following MDS or genotoxic therapy or seen with older adults.
Myeloproliferative Disorders (MPD)

Chronic myelogenous leukemia, Polycythemia vera: Essential thrombocythemia; Primary
myelofibrosis; Systemic mastocytosis
Chronic Myelogenous Leukemia (CML)

“A Myeloproliferative disorder, characterized by the presence of a BCR-ABL fusion gene.”
Origin: Pluripotent hematopoietic stem cell
Age: 50-60yrs
1) MC- Reciprocal t(9;22) translocation, designated as Philadelphia chromosome.
2) t(9;22) leads to fusion of portions of the BCR gene on chromosome 22 & the ABL gene on
chromosome 9 generating BCR-ABL fusion gene.
Pathogenesis: Genetic aberrations drive the proliferation of granulocytic & megakaryocytic
progenitors, and also causes abnormal release of immature granulocytic forms into the blood.
Diagnosis:
I) Bone marrow: 1) Hypercellular marrow with elevated myeloid & megakaryocytic series
of cells. Erythroid series is either unaffected or may show mild suppression.
2) Sea-blue histiocytes (scattered macrophages with abundant wrinkled green-blue
cytoplasm) are seen with increased deposition of reticulin.
II) Peripheral smear:
1) Anemia, leucocytosis (>100,000/cmm) with shift to left having few myeloblasts (<10%) &
thrombocytosis.
2) Eosinophilia & basophilia are seen.
III) Karyotyping: Detects the BCR-ABL fusion gene.
IV) C/P: 1) Fatigue, weakness, weight loss & anorexia .
2) Splenomegaly; Mild hepatomegaly; Lymphadenopathy
Course: 1) Chronic phase: A stable phase which may last for 3yrs
2) Accelerated phase: Increasing anemia & thrombocytopenia are seen after a period of 3yrs
in 50% of patients.
3) Blast crisis: Transformation to an acute leukemia like picture is seen having many blast
forms with or without a preceding accelerated phase. In 70% of cases, blasts are of myeloid
origin (myeloid blast crisis) & in the reminder the blasts are of pre-B cell origin (lymphoid
blast crisis).
Juvenile Myelomonocytic Leukemia (Juvenile Chronic

Myelogenous Leukemia)
It is grouped under MDS / MPD
Age: <4yrs
Association: Neurofibromatosis 1 (NF 1)
Genetic alterations: Monosomy 7 may be associated. No Philadelphia chromosome seen.
Bone marrow: Hypercellular marrow with increased myeloid series of cells.
Peripheral smear: Anemia, leukocytosis with neutrophilia & monocytosis and
thrombocytopenia. Few myeloblasts & nucleated RBCs are seen
C/P: Failure to thrive, pallor, fever, hepatosplenomegaly, lymphadenopathy, skin rashes &
bleeding manifestations.
Leukemoid Reaction
“It refers to presence of markedly increased total leukocyte count (<50,000/cmm) with
immature cells in peripheral blood resembling leukemia.”
Causes: Severe bacterial infections (Pneumonia); Severe hemorrhage; Severe acute
hemolysis; Burns; Metastatic tumors of bone marrow
Bone marrow: Hypercellular marrow with increased myeloid series of cells
Peripheral smear: Leukocytosis (>50,000/cmm) with shift to left seen with neutrophilia.
Myeloblasts are usually absent. Basophilia is not seen.
C/P: Features of underlying disease seen
Differential diagnosis: CML
Chronic Myelogenous Leukemia Vs Leukemoid Reaction
Feature CML Leukemoid reaction

Nature Neoplastic Reactive
Clinical picture Splenomegaly Features of underlying disease
Total leukocyte count >100,000cells/cmm <50,000 cells /cmm
Myeloblasts Common Uncommon
Basophilia Present Absent
Eosinophilia Present Absent
Toxic granules in neutrophils Absent Present
NAP Score Low High
Philadelphia chromosome Present Absent
Hodgkin Lymphoma (HL)

“It arises in a single node or chain and spreads in a predictable way to anatomically
contiguous lymphoid tissue.”
WHO Classification: Nodular sclerosis; Mixed cellularity; Lymphocyte rich; Lymphocyte
depletion; Lymphocyte predominant
Classical forms: Nodular sclerosis; Mixed cellularity; Lymphocyte rich; Lymphocyte
depletion
Genetic alterations: Mutations that activate transcription factor NF-kB in classical forms
Risk factor: EBV association in classical forms
Types
I) Nodular sclerosis: MC type
Age: Young adults
Sex: M=F
EBV association: Uncommon
Morphology: Lymph node: Circumscribed nodules with bands of collagen; RS Cells –
Lacunar type; Background seen with T cells, eosinophils, plasma cells & macrophages
C/P: Painless lymphadenopathy; No systemic signs
Stage: I-II
II) Mixed cellularity

Age: Young & elderly (>55yrs)
EBV association: 70%
Morphology: Lymph nodes: Diffuse effacement with T cells, eosinophils, plasma cells &
macrophages; R-S cells - Both diagnostic & mononuclear variants
C/P: Painless lymphadenopathy with systemic signs (night sweats, fever & weight loss)
Stage: III-IV
III) Lymphocyte rich

Age: Older
Sex: M>F
Morphology: Lymph node: Diffuse effacement with reactive lymphocytes; R-S cells:
Diagnostic & mononuclear variants
Stage: I-II
IV) Lymphocyte depletion: Least common type

Age: Elderly
Sex: M>F
Risk factors: HIV infection
Morphology: Lymph node: Paucity of lymphocytes & relative abundance of R-S cells
(diagnostic & pleomorphic types).
C/P: Painless lymphadenopathy with systemic signs (Night sweats, fever & weight loss)
Stage: III-IV
V) Lymphocyte predominant
Age: <35yrs
Sex: M>F
Site: Cervical & axillary lymph nodes
EBV association: Absent
Morphology: Lymph node: Nodular infiltration with small lymphocytes & macrophages;
R-S cells: Lymphohistiocytic (L&H) variants (popcorn cells).
Stage: I-II
Spread: Lymph nodes are involved first, then spleen, liver and finally bone marrow & others.
Reed-Sternberg cells (R-S cells)
They are neoplastic giant cells, essential for the diagnosis of Hodgkin lymphoma.
Origin: Germinal center or post germinal center B cells
Role: R-S cells of classical forms secrete various factors that induce the accumulation of
reactive lymphocytes, macrophages & granulocytes.
Morphology:
Classic, diagnostic R-S cells: Large cells with multiple nuclei or a single nucleus with
multiple nuclear lobes, each with a large inclusion-like nucleolus and abundant cytoplasm.
Variants:
1) Mononuclear variants: A single nucleus with a large inclusion like nucleolus is seen.
2) Lacunar variants: Contain folded or multilobate nucleus with abundant pale cytoplasm,
often disrupted during sectioning. Seen with nodular sclerosis type.
3) Lymphohistiocytic (L&H) variants: Contain polypoid nuclei with inconspicuous
nucleoli and moderately abundant cytoplasm. Seen with lymphocyte predominance type.
Mummification: Death of R-S cells in classical forms of Hodgkin lymphoma in which, they
shrink & become pyknotic.
Clinical Staging (Ann Arbor Classification)
It involves physical examination, radiologic imaging of the abdomen, pelvis, and chest &
biopsy of the bone marrow. Staging is important for prognosis & to guide therapy.
Stage I – Involvement of a single lymph node region or a single extralymphatic organ or site.
Stage II – Involvement of 2 or more lymph node regions on the same side of the diaphragm
alone or localized involvement of an extralymphatic organ or site.
Stage III – Involvement of lymph node regions on both sides of the diaphragm without or
with localized involvement of an extralymphatic organ or site.
Stage IV – Diffuse involvement of one or more extralymphatic organs or sites with or

without lymphatic involvement.
All stages are further divided on the basis of the absence (A) or presence (B) of systemic
manifestations (fever, night sweats &/or weight loss).
Diagnosis: FNAC & biopsy of involved tissues.
Burkitt Lymphoma
“Very aggressive tumor of mature B cells that usually arises at extranodal sides.”
Cell of origin: Germinal-center B cell
Types: 1) African (endemic) Burkitt lymphoma
2) Sporadic (nonendemic) Burkitt lymphoma
3) HIV-associated Burkitt lymphoma
Age: Endemic & sporadic – Children or young adults
Risk factor: EBV association (Endemic (MC)>HIV associated>Sporadic)
Genetic alterations: Increased MYC protein levels with translocations of the MYC proto-
oncogene on chr.8 (MC – t(8;14)), promoting growth & division of cells.
Morphology: 1) Affected sites are effaced by a diffuse infiltrate of intermediate sized
lymphoid cells with round to oval nuclei, coarse chromatin, several nucleoli and a moderate
amount of cytoplasm.
2) High mitotic index & numerous apoptotic cells are seen.
3) Interspersed phagocytes with abundant clear cytoplasm give ‘starry sky’ pattern.
C/P: 1) Endemic type: Mass involving the mandible & of abdominal viscera (kidneys,
ovaries & adrenal glands).
2) Sporadic type: Mass involving ileocecum or peritoneum.
10. Red Blood Cell Disorders
10 Marks
1) One year old child is admitted with increasing pallor since the age of 2 months. On
examination, there is pallor and hepatosplenomegaly, Hb – 7.2 gm%; TLC and DLC are
within normal limits. Platelets are normal. (Jan. 2016)

b) How do you classify the disease group?
c) What is the blood picture in this disease?
d) Give the clinical picture of the disease.
Ans: Thalassemia syndrome (β-Thalassemia major)
2) A 48-year-old male presented with pallor and easy fatigability. He complains of a sore
tongue and tingling in hands and feet. His hemoglobin level was 9 gms/dL. He gives history
of undergoing partial gastrectomy 3 years ago for gastric ulcer. (July, 2015)
a) What is your diagnosis?

b) Describe the pathogenesis of this disease.
c) Describe the peripheral blood picture and bone marrow appearance in this patient.
Ans: Megaloblastic anemia (Vitamin B12 deficiency)
3) A 3-year-old child presented with pallor, growth retardation and history of repeated blood
transfusions. The child is having splenomegaly and mild jaundice. Skull X-ray showing “hair
on end (crew cut) appearance”. (July, 2012)
a) What is the most probable diagnosis?

b) Describe various laboratory investigations to establish the diagnosis.
c) Discuss pathogenesis of the disorder.
4) 35 year old female presented with fatigue, weakness, glossitis and peripheral neuropathy.
(July, 2011)

b) What special investigations we do in this case to confirm the diagnosis?
c) Describe the blood and bone marrow picture.

5) A 30-year-old pregnant lady who cherishes to eat food prepared by boiling, steaming and
frying presented with anemia, glossitis, mild icterus, history of diarrhea, loss of appetite and
lack of wellbeing. No evidence of nervous system manifestations. Her serum homocysteine
(HCYS) levels are elevated but not methyl malonic acid (MMA) Levels. (March, 2010)

b) Describe the peripheral blood and bone marrow picture.
c) Discuss the special tests in diagnosis.
Ans: Megaloblastic anemia (Folic acid deficiency)
6) 35-year-old female presented with anemia, glossitis and neurological manifestations.

(April, 2009)
a) What is your provisional diagnosis?
b) What are the laboratory investigations you do in this case?
c) How do you confirm the diagnosis?
7) 40-year-old male presented with weakness, fatigue and dyspnoea, having spoon shaped
nails complaints of recurrent bleeding piles. Hb is 2.5 gm/dl. (Oct. 2008)

b) What blood investigations should be done to confirm the diagnosis?
c) What is the test to be done on the bone marrow smear?
Ans: Iron deficiency anemia
8) A 30-year-old female presented with anemia, loss of sensation and tingling in the feet.
Examination showed smooth tongue with atrophic papillae. (Oct. 2005)

b) What is the deficiency in this condition?
c) Describe the peripheral blood picture and bone marrow picture.
9) A 3 years old girl from west Bengal presented with pallor, growth retardation and history
of repeated blood transfusions. There was malocclusion of jaws with skull X ray showing
“hair on end appearance”. There was hepatosplenomegaly. Hemoglobin was 3.5 gm/dl. (Oct.
2004)
1) What is the most probable diagnosis?

2) Describe the laboratory diagnosis of the condition.
3) Describe the pathogenesis of the condition.

10) 25 years old female with the H/O 4 months amenorrhea (4 M.A) complaining of mild
jaundice, anemia and glossitis. Discuss the causes and investigation to come to a diagnosis.
(March/April, 2003)
Ans: Megaloblastic anemia (Folic acid deficiency)
4 Marks
1) Blood and bone marrow picture in folic acid deficiency anemia. (Feb. 2017)
2) Investigations in a case of hereditary spherocytosis. (Feb. 2017)
3) Bone marrow picture of megaloblastic anemia. (July, 2016)
4) Laboratory diagnosis of iron deficiency anemia. (Jan. 2015)
5) Classification of hemolytic anemia and lab diagnosis of beta thalassemia major. (July/Aug.
2014)
6) Packed cell volume (PCV). (July, 2013)
7) Blood and bone marrow findings in aplastic anemia. (Jan. 2013)
8) Peripheral smear and bone marrow picture in megaloblastic anemia. (Jan. 2011)
9) Hematocrit. (Jan. 2011)
10) E.S.R (Aug. 2010)
11) Pathogenesis of sickle cell disease. (March/April, 2008)
12) Lab diagnosis of iron deficiency anemia. (Sep/Oct. 2007)
13) Aplastic anemia. (May, 2006)
14) ESR (April/May, 2004)
15) Packed Cell Volume. (Sep. 2003)
2 Marks
1) Mention four hemoglobinopathies seen in India. (July, 2017)

2) Classify hemolytic anemias. (July, 2017)
3) What is the blood picture in vit. B12 deficiency anemia? (Jan. 2016)
4) Name four inherited hemolytic anemias. (July, 2015)
5) Laboratory diagnosis of iron deficiency anemia. (Jan. 2015)
6) Name two (2) special stains for reticulocytes and two (2) causes of reticulocytosis. (Jan.
2014)
7) Sickling test. (Aug. 2009)
8) ESR (April, 2009)
9) Reticulocyte. (Feb. 2009)
10) Megaloblast. (May, 2007)
11) ESR (March/April, 2003)
Packed Cell Volume (PCV) or Hematocrit

“PCV is the volume occupied by the red cells when a sample of anticoagulated blood is
centrifuged.”
Uses: 1) Detection of presence or absence of either anemia or polycythemia.
2) Estimation of red cell indices
Methods of estimation: Macro method (Wintrobe method); Micro method
Causes of low PCV: Anemia; Fluid overload
Causes of raised PCV: Polycythemia; Dehydration
Reference ranges: 40-50% - Adult males; 38-45% - Adult females.
Erythrocyte Sedimentation Rate (ESR)

“ESR measures the rate of settling of erythrocytes in anticoagulated whole blood.”
Methods of estimation: Westergren method; Wintrobe method
Factors increasing ESR: Anemia; Elevated fibrinogen; Macrocytosis
Factors decreasing ESR: Polycythemia; Low fibrinogen; Microcytosis
Causes of raised ESR: Infections (TB; Bacterial endocarditis; Osteomyelitis) Inflammatory
diseases (Rheumatoid arthritis; Temporal arteritis); Acute myocardial infarction; Malignancy
Causes of low ESR: Congestive cardiac failure; Sickle cell anemia; Hereditary spherocytosis
Reference ranges: 0-15mm in 1 hr. - Males<50yrs; 0-20mm in 1 hr. - Females<50yrs.
Reticulocyte Count
“Reticulocytes are young red cells containing remnants of RNA & ribosomes but no
nucleus.”
Site of production: Bone marrow
Time required for maturation: 4 to 4.5 days
Stains used: New methylene blue, & brilliant cresyl blue
Reticulocyte %: No. of reticulocytes counted / No. of red cells counted x 100
Reference ranges: 0.5%-2.5% - adults & children
Causes of increased reticulocyte count (Reticulocytosis): Blood loss; Hemolytic anemias;
Hemoglobinopathies (Sickle cell anemia)
Causes of decreased reticulocyte count (Reticulocytopenia): Megaloblastic anemia;
Aplastic anemia; Anemia of chronic disease; Thalassemia
Anemia – Classification
I) Morphologic
1) Normocytic normochromic anemia e.g., Acute blood loss
2) Microcytic hypochromic anemia e.g., Iron deficiency anemia; Thalassemia
3) Macrocytic anemia e.g., Vit.B12 or folic acid deficiency
II) Etiologic
1) Blood loss: Acute blood loss e.g., Trauma;
Chronic blood loss e.g., Peptic ulcer; Menstruation
2) Hemolysis
i) Hereditary: Hereditary spherocytosis; G-6-PD deficiency; Pyruvate kinase deficiency;
Hemoglobinopathies – Thalassemias; Structural Hb variants (HbS, HbC, HbD, & HbE)
ii) Acquired: Autoimmune hemolytic anemia; Paroxysmal nocturnal hemoglobinuria;
Hypersplenism; Hemolytic transfusion reactions
3) Decreased red cell production: Nutritional deficiencies (Iron deficiency anemia; Vit.B12
or folic acid deficiency); Inherited defects (Fanconi anemia; Thalassemia); Aplastic anemia;
Renal failure; Anemia of chronic disease
**Hemoglobinopathies in India: Thalassemias; Structural Hb variants (HbS, HbD, & HbE)
Hereditary Spherocytosis
“Hereditary hemolytic anemia with intrinsic defects in the RBC membrane skeleton.”
Mode of inheritance: Autosomal dominant (MC)
Pathogenesis:
1) Mutations most commonly affect ankyrin, band 3 or spectrin, leading to their deficiency.
2) Destabilized lipid layer is seen with loss of membrane fragments, causing spherocytes
formation.
3) Less deformable spherocytes get trapped in splenic cords & undergo lysis.
Bone marrow: Erythroid hyperplasia is seen
Peripheral smear: Spherocytes (small RBCs with lack of central pallor) are seen.
C/P: Chronic hemolytic anemia with splenomegaly, jaundice or gall stones.
Inv.: 1) Hemogram: Hb, & PCV-Low; Raised MCHC; Raised reticulocyte count
2) Raised RBC osmotic fragility
Comp.: 1) Aplastic crisis with parvovirus B19 infection
2) Hemolytic crisis with infectious mononucleosis infection
Sickle Cell Disease

“A hereditary hemoglobinopathy.”
Mode of inheritance: Autosomal recessive disorder
Genotype: Homozygous form
Genetic alterations: Substitution of valine for glutamic acid at the 6th position of the β-
globin chain forms sickle hemoglobin (HbS).
Predisposing factors: Decreased intracellular pH; Intracellular dehydration; Inflamed
vascular beds; Microvascular beds with slow transit times.
Pathogenesis: 1) Deoxygenation favors HbS formation

2) HbS polymerizes into long, stiff chains that deform RBCs into sickle or holly-leaf shape.
3) Repeated cycles of deformation cause irreversible damage to membrane causing non
deformable RBCs with permanent sickle shape.
4) Sickle cells undergo hemolysis causing anemia.
Bone marrow: Hyperplastic marrow with erythroid hyperplasia
Peripheral smear: RBC – Sickle cells, target cells, and Howell-Jolly bodies are seen.
C/P: 1) Chronic hemolytic anemia with gall stones.
2) Impairment of growth & development
3) Vaso-occlusive crises (pain crises): Major cause of morbidity & mortality.
i) Cause severe pain in the affected regions (bones, lungs, liver, brain or penis).
ii) E.g., Acute chest syndrome; Priapism; Strokes; Hand-foot syndrome
4) Aplastic crises with parvovirus B19 infection, worsens anemia.
5) Sequestration crises with intact spleen may cause splenomegaly
6) Splenomegaly seen in early childhood but adults manifest autosplenectomy
7) Increased risk of infections with Strep. Pneumoniae & H. influenza.
Inv.: 1) Hemogram: Hb, PCV – Low; Reticulocyte count – elevated
2) Hb electrophoresis detects HbS
3) Hyperbilirubinemia
4) Prenatal diagnosis by analysis of fetal DNA
5) Sickle cell slide test
“Test used for detection of hemoglobin S.”
Principle: When red cells containing HbS are deprived of oxygen, they become sickle-
shaped.
Reagent: 2% sodium metabisulphite is used a reducing agent.
Positive test: Red cells become sickle shaped or holly-leaf shaped
False –ve result: Usage of outdated reagent; Low concentration of HbS
False +ve result: Excessive usage of reagent; Drying of wet preparation
Thalassemia Syndromes
“Inherited disorders with mutations decreasing the synthesis of α or β globin chains.”
Classification:
1) β-Thalassemias: β -Thalassemia major; β-Thalassemia intermedia; β-Thalassemia minor
2) α-Thalassemias: Silent carrier; α-Thalassemia trait; HbH disease; Hydrops fetalis
β-Thalassemias
Cause: Deficient synthesis of β globin chains
Genetic alterations: Mostly point mutations involve β-globin gene. Inherited mutations
cause either reduced synthesis (β+ mutations) or no synthesis (β0 mutations) of β-globin
chains.
Pathogenesis:
1) Decreased Hb A leads to anemia.
2) Increased unpaired α-globins form insoluble inclusions causing membrane damage. This
results in ineffective erythropoiesis marrow & extravascular hemolysis in peripheral blood.
3) Anemia results in marrow hyperplasia & extramedullary hematopoiesis (spleen, liver &
LNs).
Types
1) β thalassemia major: Severe form
Major Hb: HbF
Genotype: Homozygous form with 2 β-Thalassemia genes.
Bone marrow: 1) Massive erythroid hyperplasia
2) Expansion of marrow may cause erosion of existing cortical bone & subsequent new bone
formation. In the bones of the face & skull, this gives rise to ‘crew cut’ appearance on x-ray.
Peripheral smear: RBC – Microcytic & hypochromic; Anisopoikilocytosis; Target cells;
Basophilic stippling; Fragmented RBCs. Nucleated RBCs are also seen
C/P: Growth retardation & death; Hepatosplenomegaly & lymphadenopathy; Enlargement &
distortion of cheek bones.
Inv.: 1) Hemogram: Hb, PCV, MCV, MCH – Low; Reticulocyte count – Elevated
2) Hb electrophoresis detects β-Thalassemia
3) X-rays of skull show enlarged & distorted involved bones
4) Prenatal diagnosis by analysis of fetal DNA
Comp.: Cardiac disease with secondary hemochromatosis.
2) β-Thalassemia minor or β-Thalassemia trait: Mild form

Genotype: Heterozygous form with one β-Thalassemia gene & one normal gene.
Bone marrow: Mild erythroid hyperplasia
Peripheral smear: RBC – Microcytic & hypochromic; Basophilic stippling; Target cells
C/P: Asymptomatic or mild anemia seen.
3) β-Thalassemia intermedia: Moderately severe form
Genotype: Heterogeneous form
Megaloblastic Anemia
“Nutritional anemia with Vitamin B12 or folic acid deficiency.”
Etiology:
I) Vit.B12 deficiency: 1) Inadequate intake with vegetarianism or chronic alcoholism
2) Malabsorption due to pernicious anemia or distal ileal resection
3) Increased demand during pregnancy
II) Folic acid deficiency: 1) Inadequate intake with chronic alcoholism
3) Impaired utilization with methotrexate
4) Malabsorption due to anticonvulsant or OCP usage
Pathogenesis: 1) Vit.B12 or folic acid deficiency causes inadequate DNA synthesis.
Defective nuclear maturation leads to ineffective hematopoiesis.
2) Vit.B12 deficiency also causes abnormal myelin degradation leading to neurologic
complications.
Bone marrow: 1) Hypercellular marrow with increased hematopoietic precursors.
2) Erythroid series show megaloblastic changes. Megaloblasts are large immature cells with
deeply basophilic cytoplasm, & nucleus with a fine chromatin pattern.
2) Myeloid series show giant metamyelocytes
3) Large megakaryocytes with multilobed nuclei
4) Ineffective erythropoiesis by apoptosis of precursors
Peripheral smear:
1) RBC: Macro-ovalocytes; Anisocytosis; Poikilocytosis
2) WBC: Leukopenia; Hypersegmented neutrophils
3) Platelets: Reduced
C/P: 1) Symptoms of anemia such as fatigue, & weakness are seen.
2) Vit. B12 deficiency causes lower extremity spastic weakness & paraplegia
Inv.: 1) Hemogram: Pancytopenia may be seen. Hb, & PCV - Low; Raised MCV; Normal
MCHC; Low reticulocyte count; Low Total WBC count; Low platelet count
2) Vit. B 12 deficiency: Low serum Vit.B12 levels; Elevated serum homocysteine &
methymalonic acid (MMA); Elevated MMA in urine.
3) Folic acid deficiency: Low serum or RBC folate levels; Raised serum homocysteine levels.
Iron Deficiency Anemia

“MC nutritional anemia due to iron deficiency.”
Etiology: 1) Inadequate intake in infants
2) Malabsorption due to sprue or gastrectomy
4) Chronic blood loss due to peptic ulcer, colonic cancer or menstruation
Pathogenesis: Depletion of iron stores results in inadequate synthesis of Hb causing anemia
Bone marrow: 1) Increased erythroid progenitors.
2) Loss of stainable iron from macrophages demonstrated with Perl’s stain.
Peripheral smear: RBC: Microcytic & hypochromic; Poikilocytosis with pencil cells
C/P: Fatigue, pallor; Alopecia, koilonychia; Pica; Plummer-Vinson syndrome
Inv.: 1) Hemogram: Hb, PCV, MCV, MCH - Low
2) Iron studies: Serum iron and ferritin are low & TIBC is raised.
Aplastic Anemia
“Syndrome of chronic primary hematopoietic failure.”
Etiology: 1) Idiopathic - MC
2) Physical agents: Viral (EBV,CMV or unknown hepatitis virus); Whole body irradiation
3) Inherited: Fanconi anemia
4) Chemical agents: Alkylating agents, benzene or chloramphenicol
Pathogenesis: 1) Following exposure to environmental insults, stem cells may become
antigenically altered provoking cellular immune response.
2) Activated TH 1 cells produce IFN-g and TNF that suppress & kill hematopoietic
progenitors.
Bone marrow: Hypocellular marrow with only adipocytes, fibrous stroma & scattered
lymphocytes and plasma cells.
Peripheral smear: RBC: Slightly macrocytic
WBC: Leukopenia
Platelets: Thrombocytopenia
C/P: Weakness, pallor, dyspnea; Petechiae, ecchymosis; Fever. Splenomegaly is not seen.
Inv.: 1) Hemogram: Pancytopenia is seen. Hb, & PCV – Low; Low reticulocyte count; Low
total WBC count; Low platelet count.
2) Bone marrow aspiration & biopsy confirm the diagnosis.
11. Bleeding Disorders
10 Marks
1) A 20 year old male presented with swelling of both knees and pain for the past one week.
He gives history of similar episodes earlier. He also gives history of excessive bleeding after
minor injuries. His maternal uncle has similar complaints and has been treated by repeated
blood transfusions following excessive bleeding episodes. (July, 2016)
a) What are the possible differential diagnoses?

b) What are the laboratory investigations required for the diagnosis?
c) What is the etiopathogenesis of these disorders?
d) How will you make the final specific diagnosis?
Ans: Hemophilia A
2) An young boy came with the history of massive hemorrhage after trauma, recurrent
hemarthrosis in large joints, muscle hematomas and progressive deformities leading to
crippling. Some of the family members also suffered with identical clinical manifestations.
(Aug. 2010)
b) Discuss various laboratory investigations to confirm the diagnosis.
Ans: Hemophilia A
3) A male child presented with recurrent painful hemarthrosis and hematomas. History of
bleeding in male relatives on the maternal side of the family was available. (March/April,
2008)
b) Describe the inheritance of the disease.
c) Describe the lab. diagnosis of the disease.
d) Mention the complications following the therapy.
Ans: Hemophilia A
4) A 13 year old boy came to the hospital with painful left elbow following mild trauma few
days ago. Past history of bleeding gums given. His elder brother also had similar problem.
(March/April, 2005)

b) What important investigations should be done?
c) What is the confirmatory test?
Ans: Hemophilia A
5) 20 years old young man came with the history of massive hemorrhage after trauma,
recurrent hemarthrosis, progressive deformities leading to crippling with same type
manifestations in some of the family members. What is the probable diagnosis? Mention
various laboratory investigations with findings to make a final diagnosis. (Sep. 2003)
Ans: Hemophilia A
4 Marks
1) Tabulate the differences between hemophilia A & von Willebrand disease. (July, 2017)
2) Von Willebrand disease. (Jan. 2015)
3) von Willebrand disease. (Jan. 2012)
4) Immune thrombocytopenia. (May, 2007)
2 Marks
1) Enumerate four causes of disseminated intravascular coagulation (DIC). (Jan. 2016)

2) Prothrombin time. (Sep/Oct. 2007)
3) Bleeding time. (Oct. 2005)
Prothrombin Time
Use: To assess the extrinsic and common coagulation pathways.
Principle: The clotting of plasma is measured after addition of an exogenous source of tissue
thromboplastin and calcium ions.
Causes of prolonged PT: Liver disease; Vit. K deficiency; Treatment with oral
anticoagulants; DIC.
Reference range: 11-16 sec.
Bleeding Time
Use: To assess primary hemostasis.
Principle: A superficial skin incision is made and the time required for bleeding to stop is
measured.
Methods: Ivy’s, Duke’s and template methods.
Causes of prolonged bleeding time: Thrombocytopenia; Disorders of platelet function; von
Willebrand disease; Disorders of blood vessels.
Reference range (Ivy’s method): 2-7 min.
Chronic Immune Thrombocytopenic Purpura (ITP)

“Autoantibody mediated destruction of platelets causing thrombocytopenia.”
Age: <40yrs
Sex: F>M
Etiology: Primary or secondary.
1) Primary or idiopathic: No known risk factors.
2) Secondary: Seen with SLE, HIV or CLL.
Pathogenesis:
1) Production of autoantibodies (IgG) against platelet membrane glycoproteins IIb-IIIa or Ib-
IX. 2) Autoantibody coated platelets are phagocytosed and destroyed in spleen.
C/P: Bleeding manifestations such as petechiae, ecchymoses; Easy bruising, nosebleeds, and
bleeding from gums; Melena, hematuria or excessive menstrual flow.
Diagnosis: 1) Peripheral smear: Low platelet count with large platelets
(megathrombocytes).
2) Bone marrow: Normal or raised megakaryocytes.
3) PT & PTT: Normal
4) Tests for platelet autoantibodies.
Comp.: Subarachnoid hemorrhage & intracerebral hemorrhage.
Von Willebrand Disease

“MC inherited bleeding disorder.”
Inheritance: Autosomal dominant (MC).
Types: Type 1 & type 3: Quantitative defects in vWF.
Type 1: MC type; Autosomal dominant; Mild to moderate vWF deficiency; Mild disease.
Type 3: Autosomal recessive; Vey low levels of vWF; Severe disease.
Type 2: Qualitative defects in vWF; Autosomal dominant; Mild to moderate bleeding.

C/P: Spontaneous bleeding from mucous membranes (e.g., epistaxis), excessive bleeding
from wounds or menorrhagia.
Diagnosis: 1) Platelet count: Normal
2) vWF levels: Reduced in type 1 & 3
3) Factor VIII levels: Low in type 1 & 3
4) Prolonged PTT: Type 1 & 3
Hemophilia A (Factor VIII Deficiency)

“MC hereditary cause of serious bleeding with an abnormality of the intrinsic coagulation
pathway.”
Inheritance: X-linked recessive.
Sex: Primarily males
Cause: Sporadic or germ line mutations causing factor VIII deficiency.
Genetic alterations: Deletions, inversions & splice junction mutations.
C/P: 1) Easy bruising, massive hemorrhage after trauma or operative procedures.
2) Spontaneous bleeding into joints (hemarthrosis).
Diagnosis: 1) PTT: Prolonged
2) PT: Normal
3) Low factor VIII levels – Confirms the diagnosis.
Differential Diagnosis: Hemophilia B; Von Willebrand disease
Comp.: Joint deformities
Therapy related comp.: Development of antibodies against factor VIII, following infusions
of recombinant factor VIII.
Hemophilia B (Christmas Disease, Factor IX Deficiency)

Inheritance: X-linked recessive.
Cause: Mutations causing factor IX deficiency.
C/P: Clinically indistinguishable from Hemophilia A.
Diagnosis: Low factor IX levels confirms the diagnosis.
Hemophilia A Vs Von Willebrand Disease

Feature Hemophilia A vWD
Incidence Rare Common
Inheritance X- linked recessive AD or AR
Sex affected Primarily males Males or Females
Defect lies in Factor 8 vWF
Mucocutaneous bleeding Present Absent
Hemarthrosis Common Rare
APTT Increased Normal or Increased
Bleeding time Increased Normal
Factor VIII levels Reduced Normal or reduced
Disseminated Intravascular Coagulation (DIC)

“Acute, subacute or chronic thrombohemorrhagic disorder.”
Etiology: 1) Obstetric complications (amniotic fluid embolism, dead retained fetus) - MC
2) Cancers (adenocarcinomas of the lung & pancreas; Acute promyelocytic leukemia)
3) Sepsis (meningococcemia)
4) Tissue injury (major trauma, severe burns)
Pathogenesis: 1) Excessive activation of coagulation & formation of thrombi are seen with
the release of procoagulants (tissue factor) into the circulation & extensive endothelial injury.
2) Wide spread deposition of fibrin leads to ischemia & microangiopathic hemolytic anemia.
3) Consumption of platelets & clotting factors and the activation of plasminogen leads to
hemorrhagic diathesis.
C/P: 1) Microangiopathic hemolytic anemia, dyspnea, cyanosis & respiratory failure.
2) Convulsions & coma.
3) Oliguria, acute renal failure & shock.
Diagnosis: 1) Platelet count: Low
2) PT & PTT: Prolonged
3) Fibrinogen levels: Reduced
4) Fibrin degradation products: Elevated
Miscellaneous
Cytology
4 Marks
1) Indications for FNAC and its pitfalls. (Jan. 2016)

2) Exfoliative cytology. (Aug. 2010)
3) Indications for FNAC and its pitfalls. (Feb. 2009)
4) Exfoliative cytology. (Oct. 2008)
2 Marks
1) Significance of exfoliative cytology. (July, 2012)

2) Exfoliative cytology. (Oct. 2005)
Transfusion Medicine
2 Marks
1) Enumerate four transfusion reactions. (Feb. 2017)

2) Name 4 blood components separated from whole blood and mention one clinical use for
each. (Jan. 2013)
3) Blood transfusion reactions. (July, 2011)
4) Mode of action of anticoagulants. (Jan. 2011)
Others
4 Marks
1) Pleomorphic adenoma. (April, 2009)

2) Basal cell carcinoma. (May, 2006)
3) Pleomorphic adenoma. (Oct. 2005)
2 Marks
1) Name the tests for detection of proteins in urine. (July, 2012)

2) Frozen section. (Jan. 2012)
3) Specific gravity of urine. (Aug. 2010)
PAPER II
SYSTEMIC PATHOLOGY
12. Blood Vessels
4 Marks
1) Morphology and complications of atherosclerosis. (Feb. 2017)

2) Atherosclerotic aneurysm. (July, 2015 )
3) Pathology of Aortic dissection. (Jan. 2011)
4) Definition and types of Aneurysm. (Oct. 2008)
5) Syphilitic Aneurysm. (May, 2006)
6) Pathogenesis of Atherosclerosis. (March/April, 2005)
7) Pathogenesis of essential hypertension. (Oct. 2004)
8) Aneurysm. (March/April, 2003)
2 Marks
1) Pathogenesis of dissecting aneurysms. (July, 2017)

2) Types of aneurysms. (July, 2013)
3) Complications of atherosclerosis. (Aug. 2009)
Hypertension
Clinically significant hypertension: Sustained diastolic pressures >90mm Hg or sustained
systolic pressures >140mm Hg.
Types:
I) Essential or primary - MC
Etiology: Idiopathic
Pathogenesis:
1) Genetic factors: Polymorphisms in vasomotor tone or blood volume regulation.
2) Reduced renal sodium excretion, increases fluid volume & BP
3) Environmental factors: Stress, obesity, smoking, physical inactivity, heavy salt
consumption
4) Increased vascular resistance with vasoconstriction or structural changes in vessel walls.
II) Secondary - Rare
Etiology: Known underlying cause.
1) Renal: Renal artery stenosis, chronic renal disease
2) Endocrine: Pheochromocytoma, Cushing syndrome, Conn syndrome
3) Cardiovascular: Coarcation of aorta; Polyarteritis nodosa
Morphology: 1) Hyaline arteriolosclerosis: Homogenous, pink, hyaline thickening of
arteriolar walls with luminal narrowing. Seen with benign hypertension.
2) Hyperplastic arteriolosclerosis: Concentric, laminated (onion-skin) thickening of
arteriolar walls with luminal narrowing. Seen with severe hypertension.
C/P: Asymptomatic (MC).
Comp.: Aortic dissection, atherosclerosis, stroke, hypertensive heart disease, renal failure.
Atherosclerosis
“A form of arteriosclerosis, characterized by intimal lesions such as atheromatous plaques.”
Site: Large elastic arteries (aorta, carotid, & iliac arteries) and large & medium sized
muscular arteries (coronary & popliteal arteries)
Major risk factors:
I) Modifiable: Cigarette smoking, diabetes mellitus, hypertension, & hyperlipidemia.
II) Non-modifiable (Constitutional): Male gender, advanced age, & family history (e.g.,
familial hypercholesterolemia).
Others: Inflammation; Hyperhomocystinemia; Metabolic syndrome; Liprotein a
Pathogenesis
1) Endothelial injury & dysfunction, causing increased vascular permeability, leukocyte
adhesion, and thrombosis.
2) Accumulation of lipoproteins, mainly LDL & its oxidized forms in the vessel wall.
3) Monocyte adhesion to the endothelium, followed by migration into the intima and
transformation into macrophages & foam cells.
4) Platelet adhesion
5) Smooth muscle cell recruitment with factors released from activated platelets &
macrophages & transformation into foam cells.
6) Smooth muscle cell proliferation, extracellular matrix production, & recruitment of T cells.
7) Lipid accumulation both intracellularly & extracellularly.
Morphology
I) Fatty streak: Earliest stage
Gross Flat, yellow intimal elongated streaks
Micro.: Lipid laden macrophages (foam cells)

II) Atheroma or atheromatous plaque or fibrofatty plaque:
Gross: White or whitish-yellow, eccentric raised lesion
Micro.
1) Fibrous cap: Composed of smooth muscle cells, inflammatory cells & dense collagen.
2) Necrotic centre: Composed of dead cells, foam cells, lipid, & plasma proteins.
Fate of atheroma: Calcification; Rupture, ulceration or erosion of the surface; Intra plaque
hemorrhage.
Comp.: Myocardial infarction; Stroke; Atheroembolism; Aortic aneurysms; Mesenteric
occlusion and bowel ischemia; Ischemic encephalopathy; Peripheral vascular disease.
Aneurysms
Def.: Localized abnormal dilation of a blood vessel or the heart.
True aneurysms: Involve all the 3 layers of artery or the thinned wall of the heart.
e.g., Atherosclerotic, syphilitic, & ventricular aneurysms
Pseudo aneurysms or False aneurysms: Extravascular hematoma communicating with the
intravascular space following a wall defect. E.g., Ventricular rupture
Classification: 1) Saccular aneurysms: Spherical discrete outpouchings involving only a
portion of the vessel wall. They vary in diameter & often contain thrombus.
2) Fusiform aneurysms: Circumferential diffuse dilations involving a long vascular
segment. They vary in diameter & length. MC sites: Aortic arch, abdominal aorta.
Etiology: 1) Congenital: Berry aneurysms
2) Acquired: Atherosclerosis & hypertension (MC); Trauma; Vasculitis; Infection (Mycotic
aneurysms)
Pathogenesis: 1) Inadequate or abnormal connective tissue synthesis (e.g., Marfan syndrome;
Ehlers Danlos syndrome)
2) Excessive connective tissue degradation (e.g., Atherosclerosis)
3) Loss of smooth muscle cells or change in smooth muscle cell synthesis with cystic medial
degeneration (e.g., Atherosclerosis; Hypertension)
Abdominal Aortic Aneurysms (AAA)

“Saccular or fusiform true aneurysms.”
Age: >50 yrs
Sex: F>M
Site: Between the renal arteries & the aortic bifurcation
Predisposing factors: Smoking
Causes: Atherosclerosis (MC)
Pathogenesis:
1) Excessive connective tissue degradation, mediated by MMPs from macrophages.
2) Ischemic injury involving inner media causes cystic medial degeneration.
Morphology: 1) Extensive atherosclerosis with destruction & thinning of underlying media.
2) Bland, laminated, poorly organized mural thrombus seen in the aneurysmal sac.
C/P: Asymptomatic (MC); May present as abdominal mass.
Comp.: Rupture with hemorrhage; Embolism; Impingement on adjacent structures.
Aortic Dissection
“Formation of a blood-filled channel within the aortic wall by separating the laminar planes
of media.”
Etiology
1) Hypertension (MC): Seen in males aged 40 – 60yrs
2) Connective tissue disorders (Marfan syndrome) in younger adults
3) Iatrogenic
Pathogenesis: Intimal tear leads to blood dissecting laminar planes of media (anterograde or
retrograde) causing intramural hematoma.
Morphology: 1) Cystic medial degeneration is the most frequent pre-existing lesion.
2) Intimal tear is transverse with sharp, jagged edges.
3) Intramural dissecting hematoma between middle & outer thirds (MC).
4) Absent inflammation.
Classification:
1) Proximal lesions (Type A dissections): Most common.
Involve ascending aorta with descending aorta (DeBakey type I) or ascending aorta only
(DeBakey type II).
2) Distal lesions (Type B dissections): Begin distal to the subclavian artery without the
involvement of ascending part (DeBakey type III).
C/P: Sudden pain in the anterior chest, radiating to the back.
Comp.: Rupture, cardiac tamponade, aortic insufficiency
Syphilitic (Luetic) Aneurysms

“Cardiovascular syphilis may cause syphilitic aortitis, which may result in syphilitic
aneurysm.”
Age: >50yrs
Sex: M>F
Site: Ascending aorta & arch of aorta
Predisposing condition: Syphilitic aortitis
Pathogenesis: Endarteritis obliterans causes ischemic injury to the media resulting in
scarring.
Morphology: Gross 1) Mostly saccular in shape, varying in diameter with wrinkled intimal
surface, showing tree-bark appearance.
2) Aortic valve may show stretching & rolling of the valve-leaflets.
3) Left ventricular hypertrophy may cause cardiomegaly known as cor bovinum.
Micro. The adventitia shows fibrous thickening with endarteritis obliterans of vasa vasorum.
The fibrous scar tissue may extend into the media & the intima. Mural thrombus may be
found within the aneurysm.
C/P: Rupture with hemorrhage; Compression on adjacent structures; Cardiac dysfunction
with aortic incompetence & cardiac failure.
13. The Heart
10 Marks
1) A 59-year old man is admitted with history of chest pain of half hour duration. Pain was in
the precordial area with radiation in the left arm. Pain was severe in nature and was
accompanied by vomiting. ECG showed ST segment elevation with T wave inversion. (July,
2017)
a) What is the most likely diagnosis?

b) What biochemical investigations are useful in such a case?
c) What complications can occur?
d) What are the predisposing factors of this disease?
Ans: Myocardial infarction
2) A 68-year old man presented with left sided chest pain of one hour duration. Pain is
radiating to the left arm. ECG demonstrated ST segment elevation with T wave inversion.
(Jan. 2016)

b) Enumerate the tests you will carry out to diagnose.
c) What is the gross and microscopic picture of the lesion?
d) What are its complications?
3) 60 year old male presented with substernal pain radiating to the arms, sweating and
dyspnoea. (July, 2011)

b) Discuss the evolution of pathologic changes in this condition?
c) What are the complications?

4) An adult male patient having coarctation of the aorta and periodontal infection with habit
of vigorous brushing of teeth came to the hospital with fever and anemia. On examination
there are crops of petechiae over the skin, subungual hemorrhages, small tender cutaneous
nodules, pain in the splenic region and retinal hemorrhages. Urine examination showed
hematuria. (March, 2010)
a) What is probable diagnosis?

b) Describe etiopathogenesis and morphology of lesions in various organs involved.
c) Mention the complications.
Ans: Infective endocarditis
5) 35 year old female with history of pharyngitis 1 month back, now presented with
migratory polyarthritis and carditis. (Feb. 2009)

b) What is the pathogenesis & pathology of the lesion?
c) Discuss its sequelae.
Ans: Acute rheumatic fever
6) A 9 year old girl with history of recurrent fever, upper respiratory tract infection, arthritis,
involuntary purposeless movements of limbs was admitted with edema of feet and
breathlessness. (May, 2006)

b) Describe the etiopathogenesis.
c) Describe the morphology of the lesions.
7) 10 years old female with the H/O recurrent fever, upper respiratory tract infection and
arthritis inter ECG abnormalities. Discuss about the causes and come to correct diagnosis.
(Oct/Nov. 2002)

4 Marks
1) Valvular lesions in rheumatic heart disease. (Jan. 2015)

2) Types and morphology of cardiac vegetations. (July/Aug. 2014)
3) Cardiac lesions in acute rheumatic fever (Acute RHD). (Jan. 2014)
4) Describe location and macroscopic appearance of vegetations in bacterial endocarditis
(BE). Mention extra cardiac complications of BE. (Jan. 2013)
5) Aschoff nodules/bodies. (July, 2012)
6) Name the causes of left ventricular hypertrophy. (Jan. 2011)
7) Tetralogy of Fallot. (Aug. 2009)
8) Ascoff nodule. (April, 2009)
9) Bacterial endocarditis. (March/April, 2008)
10) Rheumatic heart disease. (Sep/Oct. 2007)
11) Aschoff bodies. (March/April, 2005)
12) Pathology of Aschoff body. (April/May, 2004)
13) Myocardial infarction. (Sep. 2003)
2 Marks
1) Mention four complications of bacterial endocarditis. (July, 2017)

2) Mention four complications of myocardial infarction. (Feb. 2017)
3) Mac Callum plaques. (Jan. 2012)
4) Enzyme study in acute myocardial infarction. (April, 2009)
5) Pancarditis. (Oct. 2008)
6) Enzyme changes in myocardial infarction. (May, 2007)
Tetralogy of Fallot
“MC cyanotic congenital heart disease with right to left shunt.”
Features: 1) VSD 2) Overriding aorta 3) Right ventricular out flow tract obstruction 4) Right
ventricular hypertrophy (RVH)
Morphology: 1) Enlarged boot shaped heart with RVH
2) Aortic valve at the superior border of large VSD
3) Subpulmonic stenosis
4) Hypoplastic pulmonary arteries
5) Large overriding aorta
C/P: Early cyanosis; Clubbing of digits; Polycythemia; Paradoxical embolism
Myocardial Infarction (Heart Attack)

“Death of cardiac muscle with prolonged severe ischemia due to coronary artery occlusion.”
Arterial trunks involved:
1) Left anterior descending coronary artery – MC
2) Right coronary artery
3) Left circumflex coronary artery
Risk factors: Advancing age, atherosclerosis, middle aged males, post-menopausal women
Pathogenesis:
1) Coronary artery atheromatous plaque undergoes an acute change with intraplaque
hemorrhage, ulceration or rupture.
2) Platelets on exposure to subendothelial collagen & necrotic plaque contents, mediate
formation of microthrobi
3) Vasospasm is stimulated with mediators released from platelets.
3) Coagulation pathway activation is seen with the release of tissue factor.
4) Complete occlusion of vessel lumen is seen with the expanded thrombus.
Patterns of infarction:
1) Transmural infarction:
Necrosis involves a portion of the left ventricular wall in its full thickness.
2) Subendocardial (nontransmural) infarction:
Necrosis involves inner 1/3rd of the ventricular wall.
3) Multifocal microinfarction:
Many intramural small necrotic foci are seen.
Morphology:
I) Reversible injury (within ½ hr): No gross or microscopic changes seen
II) Irreversible injury: Gross & microscopic changes seen after 4-12 hrs
Time Gross Microscopy
12 – 24hrs Dark mottling Coagulation necrosis
1-3 days Yellow-tan infarct appears Neutrophilic infiltration
3-7 days Yellow-tan infarct with hyperemic border Macrophages replace
neutrophils
10-14 days Red-gray infarct with depressed borders Well-established granulation
tissue
2-8 wk Gray-white scar appears Prominent collagen deposition
> 2 m. Scarring complete Dense collagenous scar
C/P: Chest pain for >30 min, crushing or squeezing in nature. Rapid, weak pulse;
Diaphoresis; Nausea & vomiting; Dyspnea.
Inv.: I) Cardiac markers: Cardiac specific troponins (T & I); CK-MB(mass); Myoglobin
1) Within 3 – 12 hrs CK-MB, Troponin T & I are elevated.
2) CK-MB & Troponin I peak at 24 hrs.
3) CK-MB returns to normal in 48-72 hrs, troponin I in 5-10 days & troponin T in 5 to 14
days.
4) Myoglobin rises within 1-3 hrs, peak at 6-9 hr & return to normal in 24 hrs.
II) ECG: 1) ST elevation is seen with transmural infarct
2) No ST elevation seen with subendocardial infarct
3) Nonspecific changes are seen with microinfarctions
Comp.: Cardiogenic shock; Arrhythmias; Myocardial rupture; Ventricular aneurysm;
Pericarditis; Cardiac failure
Rheumatic Fever (RF) & Rheumatic Heart Disease (RHD)

Rheumatic fever: It is an acute, immunologically mediated, multisystem inflammatory
disease.
Age: 5-15yrs (MC)

Causative agent: Group A streptococcus
Pathogenesis: 1) With pharyngeal or cutaneous streptococcal infection, antibodies & CD4+
T cells directed against streptococcal M proteins, cross react with host cardiac proteins.
2) Antibody binding can activate compliment & recruit inflammatory cells.
3) Cytokines produced from stimulated T cells cause macrophage activation.
Morphology:
1) Pancarditis: Pericarditis, myocarditis or endocarditis
2) Aschoff bodies: Foci of T lymphocytes, occasional plasma cells & plump activated
macrophages (Anitschkow cells) found in any layer of the heart.
Evolution: Involves 3 stages
i) Early (exudative or degenerative) stage: It is apparent by about 4th wk of illness.
Initially, there is edema of the connective tissue with increased ground substance. Later,
separated collagen fibers undergo fragmentation causing fibrinoid degeneration.
ii) Intermediate (proliferative or granulomatous) stage: It is apparent by 4th to 13th wk of
illness. Infiltration with T lymphocytes, plasma cells & Anitschkow cells seen.
Anitschkow cells: Macrophages with abundant cytoplasm & central round to ovoid nucleus
with chromatin condensed into a central, slender wavy ribbon (caterpillar cells).
iii) Late (healing or fibrous) stage: It is apparent by 12 to 16 wk after the illness. Lesions
become less cellular with an increase in collagenous tissue, forming a fibrocollagenous scar.
3) Fibrinoid necrosis within the cusps or tendinous cords.
4) Small warty vegetations (verrucae) are seen overlying necrotic foci & along lines of
closure of the valve leaflets.
Rheumatic heart disease: It is characterized by deforming fibrotic valvular disease.
Site: Mostly mitral valve is affected

Predisposing condition: Recurrent acute rheumatic carditis
Morphology:
1) Mitral valve: Shows leaflet thickening, commissural fusion and shortening, & thickening
and fusion of the corda tendinae. Mitral stenosis seen as ‘fish mouth’ or ‘buttonhole’ stenosis.
2) Mac Callum plaques: Irregular thickenings in left atrium induced by subendocardial
lesions.
3) Left atrium shows progressive dilation with mural thrombus formation.
4) Right ventricular hypertrophy is seen in late stages.
Micro: Valves show post-inflammatory neovascularization & transmural fibrosis
C/P: 1) Acute rheumatic Carditis: Pericardial friction rubs, tachycardia, and arrhythmias.
2) Chronic RHD: Murmurs; Cardiac hypertrophy & dilation; Heart failure & arrhythmias.
Jones criteria: I) Major: Migratory polyarthritis of the large joints; Pancarditis;
Subcutaneous nodules; Erythema marginatum of the skin; Sydenham chorea
II) Minor: Fever; Arthralgia; Elevated acute phase reactants in blood
Diagnosis: Evidence of a preceding Group A streptococcal infection, with 2 major or 1 major
& 2 minor manifestations.
Inv.: Pharyngeal cultures; Antibodies to streptococcal enzymes (streptolysin O & DNase B)
Comp.: Thromboembolic complications & infective endocarditis.
Infective Endocarditis (IE)

“Microbial infection of the heart valves or the mural endocardium with the formation of
vegetations.”
Cause: Bacteria (MC)
Risk factors
1) Valvular: RHD with valvular scarring, mitral valve prolapse, bicuspid aortic valve
2) Bacteremia: IVDA, dental or surgical procedures
Predisposing conditions: Neutropenia; Malignancy; Immunosuppression; Diabetes mellitus
Types: Acute IE and subacute IE
Feature Acute IE Sub acute IE
Onset: Acute Insidious
Heart valve Normal Abnormal
Bacteria: Highly virulent (Staph. Aureus) Low virulent (Strep. viridans)
Vegetations Large Small
Lesions More destructive Less destructive
Embolization More likely Less likely
Prognosis Poor Good
Morphology: 1) Single or multiple, friable, bulky & destructive vegetations are seen
involving one or more valves (MC-Mitral or aortic valves).
2) Vegetations are composed of fibrin, inflammatory cells & microbes.
3) Ring abscesses may be formed in acute IE with myocardial erosion.
4) Subacute IE shows healing with granulation tissue & fibrosis.
C/P: Fever, chills, weakness, fatigue, loss of weight & a flu like syndrome; Murmurs.
Comp.: Splinter or subungual hemorrhages;
Janeway lesions (Erythematous or hemorrhagic nontender lesions on the palms or soles);
Osler nodes (Subcutaneous tender nodules in the pulp of digits);
Roth spots (Retinal hemorrhages); Glomerulonephritis; Arrhythmias; Septic infarcts
Diagnosis: Biopsy; Blood culture; Echocardiography
Vegetations
“Thrombi on heart valves are called vegetations, which can be infected or sterile.”
Disorders with vegetations:
1) Rheumatic heart disease (RHD)
i) Gross: Small warty vegetations are seen along the lines of closure of the valve leaflets.
ii) Micro: Fibrinoid necrosis within the cusps or tendinous cords with overlying infected
thrombi
iii) Deforming fibrotic valvular disease is associated.
2) Infective endocarditis (IE)

i) Gross: Large, single or multiple, friable & destructive vegetations are seen on the valve
cusps that can extend onto the chordae.
ii) Miro. Infected thrombi composed of fibrin, inflammatory cells & microbes.
iii) Vegetations are prone to embolization.
3) Nonbacterial thrombotic endocarditis (NBTE)

i) Gross: Small, single or multiple vegetations are seen, located usually along the line of
closure of the valve leaflets.
ii) Micro. Bland thrombi are seen loosely attached to the underlying valve.
iii) They are non-invasive & do not elicit any inflammatory reaction.
4) Endocarditis of SLE (Libman-Sacks endocarditis)

i) Gross: Small, single or multiple, pink vegetations are seen with warty appearance located
on either or both sides of the valve leaflets.
ii) Micro. Bland thrombi are seen composed of finely granular fibrinous eosinophilic
material
iii) Valvulitis is seen associated.
Left Ventricular Hypertrophy

Causes: Hypertension (MC cause); Aortic valve stenosis; Hypertrophic cardiomyopathy;
Athletic training; Congenital heart disease.
14. The Lung
10 Marks
1) A 55 year old lady presents with breathlessness and cough for the past 2 weeks. She gives
history of loss of weight and tiredness for past 6 months. X-ray chest revealed a massive
pleural effusion on the left side. CT scan showed a nodular mass which is peripherally
located in the left lung. CT guided biopsy of the mass showed, large cells with pleomorphic
nuclei and prominent nucleoli, arranged in a glandular pattern. (Jan. 2015)

b) Mention the histological types (sub-classification) of this lesion with illustrations.
c) Describe it’s etiopathogenesis.
Ans: Lung carcinoma
2) A male aged 60 years who is a chronic smoker presented with history of slowly increasing
severe exertional dyspnoea and weight loss. He is barrel-chested and dyspneic with
prolonged expiration, sits forward in a hunched-over position and breaths through pursed
lips. (Jan. 2014)

b) Mention the major types (classification) with appropriate diagrams.
c) Discuss the pathogenesis of the lesion.
d) Mention two causes of death in most of these patients.
Ans: Emphysema
3) An elderly male, chronic smoker presented with steadily progressive dyspnoea. On

examination he was found to be barrel chested and dyspnoeic with prolonged expiration, sits
forward in a hunched over position and breaths through pursed lips. Chest X-ray revealed
hyperinflation and small heart. (May, 2007)

b) Explain the role of smoking in the causation of the disease?
c) Describe the morphology of the organ involved?
d) List the complications.
Ans: Emphysema
4) 60 years old man habituated to tobacco smoking came with history of cough, hemoptysis,
dyspnoea, loss of weight, severe pain in the distribution of the ulnar nerve and Horner’s
syndrome. Mention various laboratory investigations to make a final diagnosis. Describe the
pathology of the lesion. (Sep. 2003)
Ans: Lung carcinoma

4 Marks
1) Classify pneumonia. What are the stages of lobar pneumonia? (July, 2017)
2) Pathogenesis of bronchial asthma. (July, 2016)
3) Asbestosis. (Jan. 2016)
4) Morphology of lobar pneumonia and complications. (July, 2015)
5) What are the types of pneumonia; write about the morphology of lobar pneumonia and its
complications. (July/Aug. 2014)
6) Lobar pneumonia. (July, 2013)
7) Etiopathogenesis of emphysema. (Jan. 2013)
8) Morphology of lobar pneumonia. (Jan. 2012)
9) Bronchiectasis. (July, 2011)
10) Gross and microscopic picture of lobar pneumonia. (Aug. 2010)
11) Mesothelioma. (Aug. 2009)
12) Asbestosis. (Feb. 2009)
13) Stages of lobar pneumonia. (Oct. 2008)
14) Bronchiectasis. (March/April, 2008)
15) Asbestosis. (May, 2006)
16) Lung abscess. (May, 2006)
17) Broncho pneumonia. (Oct. 2005)
18) Bronchiectasis. (March/April, 2005)
19) Emphysema-Definition, types & etiology. (Oct. 2004)
20) Lung abscess. (April/May, 2004)
21) Lung abscess. (March/April, 2003)
22) Emphysema. (Oct/Nov. 2002)
2 Marks
1) Name any four causes of carcinoma lung. (Feb. 2017)

2) Lung cancer-Histological types. (July, 2012)
3) Name the histologic variants of carcinoma lung. (Jan. 2011)
4) Lung abscess. (April, 2009)
5) Stages of lobar pneumonia. (Oct. 2008)
6) Classification of bronchogenic carcinoma. (Sep/Oct. 2007)
7) Mesothelioma. (Oct. 2005)
8) Complications of lobar pneumonia. (March/April, 2005)
Emphysema
Def.: Irreversible enlargement of the air spaces distal to the terminal bronchiole.
Classification:
1) Centriacinar (centrilobular): MC form; Central or proximal parts of acini are affected.
Associated with smoking. MC in the upper lobes.
2) Panacinar (panlobular): Entire acinus is affected. Associated with alfa 1 anti trypsin
deficiency. MC in lower zones of lungs
3) Distal acinar (paraseptal): Distal portion of acinus is affected. Seen with spontaneous
pneumothorax in young adults. Seen adjacent to the pleura, along the lobular connective
tissue septa.
4) Irregular: Irregular involvement of acinus. Associated with scarring.
Etiology: 1) Cigarette smoking 2) Alfa 1-anti trypsin deficiency
Pathogenesis:
1) Inflammatory mediators: Epithelial cells & inflammatory cells release mediators (LTB4,
IL-8, TNF) which further amplify inflammatory process & induce structural changes.
2) Protease-antiprotease imbalance: Release of several proteases from inflammatory cells
& epithelial cells with relative deficiency of antiproteases results in tissue damage.
3) Oxidative stress: Oxidants produced from inflammatory cells, substances in tobacco
smoke causing tissue damage
4) Infection: Bacterial or viral infections may exacerbate the associated inflammation.
Morphology: Gross Voluminous lungs; C/S: large alveoli
Micro. Thin septa separates abnormally large alveoli with only focal centriacinar fibrosis;
Decrease in capillary bed area.
C/P: Dyspnea, cough, wheezing, weight loss; Patient is barrel-chested, sits forward in a
hunched-over position, and breathes through pursed lips.
Comp.: Cor pulmonale, congestive cardiac failure
Causes of death: Coronary artery disease; Respiratory failure; Right-sided heart failure
Asthma
“It is a chronic relapsing inflammatory disorder, characterized by paroxysmal reversible
bronchospasm.”
Types
I) Atopic asthma: MC type
Age: Childhood
Family history: Positive
Stimuli: Environmental allergens (pollen, dusts, animal dander & foods)
Evidence of allergen sensitization: Present
Aggravating factors: Respiratory viral infections
Associations: Allergic rhinitis & eczema
Mechanism: Type I hypersensitivity reaction
Pathogenesis: Immune responses to environmental allergens in genetically predisposed
individuals cause atopic asthma.
1) Genetic susceptibility: Individuals with IL-13 gene polymorphisms are at greater risk.
2) Environmental factors: Exposure to airborne pollutants play a crucial role.
3) Immune responses:
i) Exaggerated TH2 response is seen with secretion of cytokines (IL-4, IL-5, IL-13) that
promote inflammation & stimulate IgE production from B cells.
ii) IgE binds to the Fc receptors on submucosal mast cells, and repeat exposure to allergen
trigger the mast cells to release granule contents & produce various mediators.
iii) Early-phase reaction: Bronchoconstriction, increased mucus production, vasodilation &
increased vascular permeability are seen.
Mediators & effects:
a) Leukotrienes C4, D4 & E4: Bronchoconstriction, increased vascular permeability &
increased mucus secretion.
b) Acetylcholine: Constriction of airway smooth muscle
c) Histamine: Bronchoconstriction
c) Prostaglandin D2: Bronchoconstriction & vasodilation
d) Platelet-activating factor: Platelet aggregation
iv) Late-phase reaction: Recruitment of leukocytes, eosinophils, neutrophils & T
lymphocytes is seen.
II) Non-atopic asthma

No evidence of allergen sensitization is seen, and positive family history is rare.
Predisposing factors: Respiratory viral infections (Rhinovirus, parainfluenza virus, RSV);
Inhaled air pollutants (smoking, ozone), exposure to cold & exercise.
Morphology:
Gross Lungs are overinflated with patchy atelectasis & mucus plugging of airways.
Micro. 1) Whorled mucus plugs (Curschmann spirals) & cystalloid eosinophil granular
debris (Charcot-Leyden crystals) deposit in airways.
2) Airways remodelling is seen with subbasement membrane fibrosis, an increase in the size
of submucosal glands & no. of airway goblet cells and hypertrophy &/or hyperplasia of the
bronchial muscle.
C/P: 1) Recurrent episodes of chest tightness, wheezing, dyspnoea, & cough particularly at
night and/or in the early morning.
2) Acute severe asthma (status asthmaticus): It is a state of unremitting attacks which may
lead to cyanosis and death.
Inv.: 1) Eosinophilia
2) Finding of eosinophils, Curschmann spirals, & Charcot-Leyden crystals in the sputum.
3) High total serum IgE levels in atopic asthma
Bronchiectasis
“Permanent dilation of bronchi & bronchioles with destruction of smooth muscle and elastic
tissue.”
Site: Lower lobes (B/L)
Etiology: Infections ( Bacterial, viral or fungal); Bronchial obstruction (Tumor, foreign
body); Hereditary conditions (Cystic fibrosis, Kartagener syndrome); Idiopathic
Pathogenesis: Obstruction & infection are the major contributing factors. Obstruction leads
to retention of secretions resulting in secondary infections with inflammation. Severe
infections cause necrosis and destruction of smooth muscle and elastic tissue.
Morphology: Gross Cystic dilated airways with mucopurulent secretions
Micro. Bronchi & bronchioles show inflammatory exudates with necrosis. Chronicity shows
fibrosis of the walls of bronchi & bronchioles.
C/P: Persistent cough with foul smelling sputum; Dyspnea, orthopnea or hemoptysis may be
seen.
Comp.: Cor pulmonale, brain abscess, amyloidosis
Asbestosis
It is characterized by pulmonary interstitial fibrosis with an exposure to asbestos.
Asbestos is a family of fibrous silicates. It occurs in 2 geometric forms, serpentine (flexible,
curved) & amphibole (straight, stiff). Amphiboles are more pathogenic than serpentine fibers.
Site: Begins usually in lower lobes & subpleurally
Risk factor: Smoking
Pathogenesis:
1) Amphiboles reach the deep lung, where they can penetrate the epithelial cells and reach
the Interstitium.
2) Macrophages ingest inhaled fibers, leading to inflammasome activation and production of
mediators (fibrogenic growth factors & cytokines).
3) Long term deposition of fibers & persistent release of mediators lead to generalized
interstitial pulmonary inflammation and interstitial fibrosis.
Morphology: 1) Diffuse interstitial fibrosis: Fibrosis cause enlarged air spaces enclosed
within thick fibrous walls, giving a honeycomb pattern to the affected regions
2) Asbestos bodies: Ingested fibres coated by iron-containing proteinaceous material to form
characteristic, golden brown beaded, dumbbell-shaped fibers.
3) Ferruginous bodies: Other inorganic particulates encrusted with iron.
C/P: Dyspnea; Productive cough may be present
Comp.: Respiratory failure or cor pulmonale; Lung or pleural cancer
Inv.: Chest X-ray
Pneumonia
Def.: Any infection of the lung parenchyma is known as pneumonia.
Classification: Community-acquired acute pneumonia; Health care-associated pneumonia;
Hospital-acquired pneumonia; Aspiration pneumonia; Chronic pneumonia
Community acquired Bacterial pneumonia
Predisposing factors: Extremes of age; Chronic disease (COPD, Diabetes);

Immunodeficiency; Dysfunctional spleen
Causes: Streptococcus pneumoniae (MC); H. influenza; Staph. aureus; Klebsiella
pneumoniae; Pseudomonas aeruginosa
Types: Lobar pneumonia & bronchopneumonia
I) Bronchopneumonia
Patchy consolidation of lung, often multilobar and frequently B/L & basal.
Morphology: Gross Lesions are slightly elevated, dry, granular, gray-red to yellow
Micro. Suppurative inflammatory exudate filling bronchi, bronchioles and adjacent alveoli.
II) Lobar pneumonia

Consolidation of a large portion of lobe or of an entire lobe
Stages: 1) Congestion: Gross Lungs are heavy & red
Micro. Congestion with intra alveolar fluid with many bacteria
2) Red hepatization: Gross Lungs are red, firm and airless with liver-like consistency
Micro. Exudate in alveoli with neutrophils ,RBCs, & fibrin
3) Gray hepatization: Gross Lungs look grayish brown

Micro Fibrinosuppurative exudate with disintegration of RBCs
4) Resolution: Clearing of exudates is seen.
C/P: High fever with chills, weight loss, cough with mucopurulent sputum
Comp.: Lung abscess; Empyema; Endocarditis; Meningitis
Lung Abscess
Organisms: Streptococci & Staph. aureus
Predisposing conditions: Oropharyngeal surgical or dental procedure; Sinobronchial
infections; Bronchiectasis
Routes of spread: Aspiration of infective material (acute alcoholism, coma); Antecedent
primary lung infection (A. aureus, K. pneumoniae); Septic embolism (Infective endocarditis);
Post obstructive pneumonia (Tumors).
Morphology:
Gross Single or multiple abscesses, varying in size & may affect any part of lung.
Micro. Suppurative inflammation with liquefactive necrosis is seen. In chronic cases, a
fibrous wall is seen with fibroblast proliferation.
C/P: Cough with foul smelling sputum, fever, chest pain, weight loss, & clubbing of digits
Comp.: Brain abscess, meningitis, amyloidosis
Lung Carcinoma
MC primary tumor of lung. MC cause of cancer mortality.
Age: 40-70yrs
Classification: 1) Adenocarcinoma 2) Squamous cell carcinoma 3) Large cell carcinoma 4)
Neuroendocrine carcinoma (small cell carcinoma; Carcinoid tumor) 5) Mixed carcinomas
(Adenosquamous carcinoma)
Risk factors: Tobacco smoking (major); Exposure to ionizing radiation, asbestos, &
uranium; Air pollution.
Types:
I) Adenocarcinoma
Age: <45yrs
Sex: F>M
Genetic alterations: Gain of function mutations of EGFR & KRAS
Precursors: Atypical adenomatous hyperplasia; Adenocarcinoma in situ
Gross: Gray-white, firm peripheral tumor
Micro.: Glandular differentiation with desmoplasia. Different patterns of growth such as
acinar, papillary or mucinous are seen.
II) Squamous cell carcinoma

Sex: Men>women
Genetic alterations: Mutations of TP53 & CDKN2A & 3p deletions
Precursors: Squamous metaplasia or dysplasia & carcinoma in situ
Gross: Gray-white, firm centrally located mass. Large tumors may show foci of necrosis or
hemorrhage.
Micro.: Well or moderate or poorly differentiated squamous cell carcinoma on the basis of
presence of keratinizaton & intercellular bridges.
III) Small cell carcinoma: Most aggressive type

Origin: Neuroendocrine progenitor cells
Genetic alterations: Loss of function mutations of TP53 & RB
Gross: Pale gray, centrally located tumor
Micro.: Sheets of small cells with scant cytoplasm, ill-defined borders, and hyperchromatic
nucleus with salt & pepper chromatin. Necrosis and high mitotic rates are seen.
IV) Large cell carcinoma: Undifferentiated tumor

Gross: Gray-white, firm mass
Micro.: Large cells with moderate cytoplasm & large nuclei having prominent nucleoli.
C/P: Cough (MC), weight loss, chest pain, hemoptysis, dyspnea

Metastasis: Adrenal (MC), liver, brain; Lymph nodes.
Paraneoplastic syndromes:
1) Hypercalcemia with Squamous cell carcinoma
2) SIADH & Cushing syndrome with small cell carcinoma
3) Trousseau syndrome with adenocarcinoma
4) Hypertrophic pulmonary osteoarthropathy
5) Pancoast syndrome with Pancoast tumors (Apical lung cancers with pain in the distribution
of ulnar nerve, Horner syndrome and destruction of 1st & 2nd ribs)
Inv.: Radiological (CXR;CT;PET), Cytology (FNAC; Sputum; Bronchial lavage fluids or
brushings), Biopsy
Malignant Mesothelioma
“Primary malignant tumor of pleura.”
Origin: Mesothelial cells lining visceral or parietal pleura
Risk factor: Asbestos exposure
Genetic alterations: Deletion of tumor suppressor gene INK4a
Morphology: Gross Soft, gelatinous, grayish pink mass ensheathing the lung.
Micro. 1) Epithelioid type: Cuboidal, columnar or flattened cells forming tubular or
papillary structures.
2) Sarcomatoid type: Spindle shaped cells are seen in sheets
3) Mixed (Biphasic) type: Both epithelioid and sarcomatoid patterns are seen.
C/P: Chest pain, dyspnea, recurrent pleural effusions
Metastasis: Hilar lymph nodes, liver
15. Head and Neck
4 Marks
1) Morphology of pleomorphic adenoma of salivary gland. (July, 2015)

2) Pleomorphic adenoma. (July, 2013)
3) Pleomorphic adenoma - salivary gland. (Aug. 2010)
4) Pleomorphic adenoma. (March/April, 2003)
2 Marks
1) Name four malignant tumors of salivary glands. (Feb. 2017)

2) Leukoplakia. (Aug. 2010)
3) Warthin tumor. (March, 2010)
Leukoplakia
“Precancerous lesion of oral cavity.” A white patch or plaque that cannot be scraped off and
cannot be characterized clinically or pathologically as any other disease.
Age: 40 – 70yrs
Sex: M>F
Risk factor: Tobacco usage
Site: Buccal mucosa, floor of mouth, ventral surface of tongue.
Morphology: Gross Solitary or multiple white patches or plaques.
Micro. Spectrum of epithelial changes such as hyperkeratosis, acanthosis, dysplasia or CIS.
Comp.: Squamous cell carcinoma of oral cavity
Salivary Gland Tumors - Classification

Benign: Pleomorphic adenoma; Warthin tumor; Oncocytoma; Basal cell adenoma
Malignant: Mucoepidermoid carcinoma; Adenocarcinoma (NOS); Acinic cell carcinoma;
Adenoid cystic carcinoma
Pleomorphic Adenoma (Benign Mixed Tumor)

Benign tumor of salivary glands. MC salivary gland tumor.
Age: 50-70s
Sex: F>M
Site: Parotid (MC)
Risk factor: Radiation exposure
Genetic alterations: Overexpression of the gene PLAG 1
Morphology: Gross Well circumscribed round encapsulated mass of varying size.
C/S – Gray-white with myxoid & blue translucent areas of chondroid
Micro. Epithelial (ductal or myoepithelial) elements are seen arranged in ducts, acini, strands
or sheets and are dispersed within a mesenchyme-like background of loose myxoid tissue
with islands of cartilage or bone.
C/P: Painless slow-growing mobile discrete mass
Comp.: Carcinoma ex pleomorphic adenoma
Warthin Tumor (Papillary Cystadenoma Lymphomatosum)

“Benign tumor of salivary glands.” 2nd MC salivary gland tumor.
Site: Parotid gland
Sex: M>F
Age: 50-70s
Risk factor: Smoking
Morphology: Gross Round to oval encapsulated mass of varying size.
C/S – Pale gray with cleftlike spaces filled with serous or mucinous secretions.
Micro. 1) Double layered epithelium: Upper layer of palisading columnar cells with
oncocytic change & dispersed secretory cells & lower layer of cuboidal to polygonal cells.
2) Subepithelial dense lymphoid stroma.
C/P: Discrete mass in front of & below the ear
16. The Gastrointestinal Tract
10 Marks
1) An elderly male presented with history of bleeding per rectum, altered bowel habits, loss
of appetite, loss of weight and crampy lower quadrant discomfort in the abdomen.
Hematological evaluation revealed iron deficiency anemia. What is your diagnosis? (Feb.
2017)
a) Discuss the etiopathogenesis of this disease.

b) Describe the morphology of this lesion.
Ans: Adenocarcinoma of colon
2) A 58 year old male labourer presented with history of epigastric pain occurring
immediately and sometimes within two hours of taking food. The pain relieved by vomiting.
He had good appetite but afraid to eat and used to take bland diet. There is significant loss of
body weight and deep tenderness present in the midline of epigastrium. (Jan. 2012)

b) Discuss the etiopathogenesis.
c) Describe the morphology of the lesion.
d) Mention the complications.
Ans: Peptic ulcer disease
3) A 48 years old male presented with weight loss, anorexia, vomiting and mass in the
epigastric region. On investigation, he was detected to have rigid, thickened leather bottle
stomach and a space occupying lesion in the liver. (Sep/Oct. 2007)

b) What are the factors associated with the causation of the condition?
c) Describe the morphology of the organ involved.
d) Describe the mode of spread.
Ans: Gastric adenocarcinoma
4) A 50 year old businessman complained of burning pain in the upper abdomen and
retrosternal region for a long time. The pain worsened at nights and occurred 3 hours after
meals. Pain was relieved with food. (Oct. 2004)

b) What is the etiopathogenesis?
c) Describe the pathology & complications.
Ans: Peptic ulcer disease

4 Marks
1) Pathogenesis of peptic ulcer. (July, 2017)

2) Gastric carcinoma – Location, types and metastasis. (Jan. 2016)
3) Etiopathogenesis of carcinoma stomach. (Jan. 2015)
4) What are the causes of peptic ulcer, write its morphology and complications? (July/Aug.
2014)
5) Crohn disease – Morphology. (July, 2012)
6) Crohn disease. (Aug. 2009)
7) Ulcerative colitis. (April, 2009)
8) Morphology of chronic gastric ulcer. (Oct. 2008)
9) Ulcerative colitis. (May, 2007)
10) Ulcerative colitis. (May, 2006)
11) Amoebiasis. (May, 2006)
12) Ulcerative colitis. (March/April, 2005)
13) Gross and histologic classification of gastric carcinoma. (April/May, 2004)
14) Primary malabsorption syndromes. (Sep. 2003)
15) Precancerous lesions of G.I.T. (Oct./Nov. 2002)
2 Marks
1) Complications of peptic ulcer. (July, 2016)

2) What are the four precancerous lesions of large intestine? (Jan. 2016)
3) Microscopic appearance of peptic ulcer. (July, 2015)
4) Four differences between Crohn’s disease and ulcerative colitis. (July, 2015)
5) Morphology of amoebic colitis. (Jan. 2014)
6) Four (4) complications of chronic gastric ulcer. (July, 2013)
7) Cause and histology of Barrett esophagus. (Jan. 2013)
8) Chronic gastric ulcer. (July, 2011)
9) Various sites of chronic peptic ulcer. (March, 2010)
10) Barrett esophagus. (Feb. 2009)
11) Barrett esophagus. (March/April, 2008)
12) Barrett esophagus. (Oct. 2008)
13) Barrett esophagus. (May, 2006 )
14) Microscopic picture of chronic gastric ulcer. (May, 2006)
15) Complications of gastric ulcer. (March/April, 2005)
16) Crohn disease. (March/April, 2003)
17) Barrett esophagitis. (March/April, 2003)
Barrett Esophagus
Age: 40-60s
Classification: Long segment – 3cm or more; Short segment - < 3 cm
Risk factor: Chronic GERD
Morphology: Gross One or several patches of red velvety mucosa extending upward from
grastroesophageal junction.
Micro. Intestinal type metaplasia: Columnar epithelium with goblet cells replacing
esophageal squamous epithelium.
Inv.: Endoscopy; Biopsy
Comp.: Dysplasia; Esophageal adenocarcinoma
Peptic Ulcer Disease (PUD)

“Chronic mucosal ulceration affecting the duodenum or stomach.”
Site: Stomach (along lesser curvature near the interface of the body & antrum);
Duodenum (anterior wall of proximal duodenum).
Risk factors: H. pylori; NSAIDs; Cigarette smoking; COPD; Alcoholic cirrhosis;
Drugs (Cocaine); Zollinger-Ellison syndrome
Predisposing conditions: Chronic gastritis
Pathogenesis: Imbalances between mucosal defense mechanisms (surface mucus secretion,
bicarbonate secretion into mucus & elaboration of prostaglandins) and damaging factors
(gastric acidity & peptic enzymes).
Morphology:
Gross 1) Round to oval, mostly solitary, punched-out defects seen as shallow or deep ulcers.
2) Margins of ulcer level with surrounding mucosa & base is smooth and clean.
3) Hemorrhage & fibrin deposition are seen on gastric serosa.
Micro. 1) Active ulcers show neutrophilic infiltrates
2) Healing involves granulation tissue with mononuclear cells & formation of a fibrous scar.
C/P: Epigastric burning or pain. The pain tends to occur 1-3hrs after meals during the day, is
worse at night, and is relieved by alkali or food. Nausea, vomiting, bloating, & weight loss
are seen.
Comp.: Bleeding with iron deficiency anemia; Perforation; Obstruction; Rare malignant
transformation.
Gastric Adenocarcinoma
“MC malignancy of the stomach.”
Site: Antrum (MC)
Types: Intestinal type & diffuse type
Sex: Intestinal type – M>F; Diffuse type – M=F
Risk factors: Geographic influences (MC in Japan); Low socioeconomic status; Carcinogens
(Benzopyrene)
Precursor conditions: Gastric dysplasia & adenoma for intestinal type
Etiology: Sporadic or hereditary
1) Diffuse type: Loss of function mutations in gene CDH1, which encodes E-cadherin
2) Intestinal type: Loss of function mutations involving APC gene & gain of function
mutations involving gene encoding beta-catenin.
3) Both types: Loss of function mutations involving TP53

Morphology:
1) Intestinal type: Gross Exophytic mass or ulcerative tumor
Micro. Glandular structures form adenocarcinoma
2) Diffuse type: Gross Thickened, rigid wall with diffuse rugal flattening imparting leather
bottle appearance (linitis plastica).
Micro. Discohesive cells are seen infiltrating the wall having signet ring cell morphology.
Desmoplasia is seen with no gland formation.
C/P: Early: Dyspepsia, dysphagia & nausea. Late: Weight loss, anorexia, early satiety,
anemia & hemorrhage.
Spread: i) Local invasion: Duodenum, pancreas & retroperitoneum
ii) Metastasis: Supraclavicular sentinel node (Virchow node); Periumbilical lymph nodes
(Sister Mary Joseph nodule); Left axillary lymph node (Irish node); Ovary (Krukenberg
tumor); Pouch of Douglas (Blumer shelf).
Amoebiasis
Causative agent: Entamoeba histolytica (protozoan)
Route of transmission: Fecal-oral
Sites: Caecum & ascending colon
Pathogenesis: After reaching colon, cysts colonize the epithelial surface & release
trophozoites. They attach to the colonic epithelium, invade crypts & burrow laterally into the
lamina propria. Ulcers are formed as a result of tissue damage.
Morphology: Gross Flask shaped ulcers are seen with narrow neck & broad base
Micro. Extensive liquefactive necrosis with few inflammatory cells.
C/P: Abdominal pain, bloody diarrhea & weight loss
Comp.: Ameobic liver abscess; Acute necrotizing colitis; Megacolon
Inv.: Intestinal biopsy; Stool exam.
Inflammatory Bowel Disease (IBD)

“A chronic disorder resulting from inappropriate mucosal immune activation.”
Components: Crohn disease & ulcerative colitis
Age: Teens & early 20s
Etiopathogenesis:
1) Inappropriate immune responses to intestinal microbiota: Seen with NOD2 polymorphisms
in Crohn disease.
2) Aberrant mucosal immune responses: TH17 T cells and production of TNF, IL-10, IL-23 &
TGF-beta play a role in IBD.
3) Intestinal epithelial dysfunction: Seen with NOD2 polymorphisms in Crohn disease and
ECM1 & HNFA polymorphisms in ulcerative colitis.
4) Altered composition of the gut microbiome: Anti-flagellin antibodies are seen associated
with Crohn disease.
Crohn Disease (Regional Enteritis)

Sites: Terminal ileum, ileocecal valve & cecum (any area of GIT).
Morphology:
Gross 1) Many mucosal aphthous ulcers coalesce & form elongated, serpentine ulcers
oriented along the axis of the bowel.
2) Patchy distribution of disease with depressed diseased mucosa & interspersed normal
mucosa gives cobble stone appearance. Skip lesions are seen.
3) Fissures & fistulous tracts may develop.
4) Intestinal wall is thickened &rubbery.
5) Stricture formation is seen
Micro. 1) Transmural involvement seen with ulceration.
2) Cryptitis, crypt abscess & crypt destruction are seen.
3) Distorted mucosal architecture with pseudo pyloric metaplasia.
4) Noncaseating granulomas are seen.
5) Mucosal atrophy with loss of crypts appears late.
C/P: Intermittent attacks of relatively mild diarrhea, fever, & abdominal pain.
Extraintestinal manifestations: Uveitis, migratory polyarthritis, sacroilitis, ankylosing
spondylitis, primary sclerosing cholangitis
Comp.: Hypoalbuminemia; Malabsorption; Carcinoma of colon
Ulcerative Colitis
Sites: Colon & rectum
Morphology:
Gross 1) Mucosa may appear red & granular or with extensive, broad-based ulcers aligned
along the long axis of intestine.
2) Diffuse involvement is seen with no skip lesions.
3) Isolated islands of regenerating mucosa (pseudopolyps) seen bulging into the lumen, with
their tips may be joined to form mucosal bridges.
4) Mucosal atrophy is seen in late stages, with a flat & smooth surface.
5) Mural thickening is not present & the serosal surface is normal.
6) No stricture formation seen.
7) Colonic dilation & toxic megacolon may be seen.
Micro. 1) Inflammatory process is diffuse and limited to mucosa & superficial submucosa.
2) Inflammatory infiltrates, crypt abscesses, crypt distortion, & pseudopyloric epithelial
metaplasia are seen.
3) Ulcers may be seen limited by muscularis.
4) Submucosal fibrosis, mucosal atrophy and distorted mucosal architecture are seen late.
5) No granulomas seen.
C/P: Attacks of bloody diarrhea with stringy, mucoid material, lower abdominal pain, &
cramps.
Extraintestinal manifestations: Migratory polyarthritis, sacroiliitis, ankylosing spondylitis,
uveitis, primary sclerosing cholangitis.
Comp.: Carcinoma of colon
Crohn Disease Vs Ulcerative Colitis

Feature Crohn disease Ulcerative colitis
Bowel region Any area of GIT Colon only
Distribution Skip lesions Diffuse
Stricture Present Rare
Inflammation Transmural Mucosal only
Ulcers Deep, knife-like Superficial, broad-based
Fibrosis Marked Mild to none
Serositis Marked Mild to none
Granulomas Seen Not seen
Fistulae/sinuses Seen Not seen
Toxic megacolon Not seen Seen
Adenocarcinoma of Colon
“MC malignancy of the GIT.”
Risk factors: 1) Advancing age: Peak incidence at 60-70yrs
2) Geographic influences: High incidence in North America
3) Dietary factors: Low intake of unabsorbable vegetable fiber & high intake of refined
corbohydrates and fat.
Precursors: Inflammatory bowel disease; Colonic adenomas; Peutz-Jeghers syndrome;
Juvenile polyposis
Etiology: Sporadic or familial. Familial cases such as familial adenomatous polyposis (FAP)
& HNPCC are seen with autosomal dominant transmission.
I) Adenoma-carcinoma sequence:
1) It involves mutations in gene APC causing activation of APC/beta-catenin pathway.
2) With loss of APC function, beta-catenin accumulates & activates genes MYC and cyclin
D1, which promote proliferation.
3) Alterations of TGF-beta signaling with loss of function mutations in genes encoding
SMAD2 & SMAD4 may allow unrestrained cell growth.
4) Activating mutations in KRAS, promote growth & prevent apoptosis.
5) Loss of function mutations in TP53 causing chromosomal instability.
II) Microsatellite instability:
1) With DNA mismatch repair deficiency, mutations accumulate in microsatellite repeats.
2) Mutations of genes encoding type II TGF-beta receptor leads to uncontrolled cell growth
3) Mutations of genes encoding pro-apoptotic protein BAX leads to its loss, enhancing the
survival of genetically abnormal clones.
III) CpG island hypermethylation phenotype (CIMP):
1) Seen with a subset of microsatellite unstable colon cancers without mutations in DNA
mismatch repair enzymes.
2) Hypermethylation of MLH1 promoter region reduces its expression & repair function.
3) Activating mutations in the oncogene BRAF, promote cell proliferation.
Morphology
Gross 1) Proximal colon cancers form polypoid exophytic masses
2) Distal colon cancers present as annular lesions, that produce napkin-ring constrictions.
Micro. 1) Well differentiated to poorly differentiated adenocarcinomas
2) Desmoplastic response is seen
3) Some tumors may be seen with signet-ring cells or display neuroendocrine differentiation.
C/P: 1) Right-sided colon cancers: Fatigue & weakness due to iron deficiency anemia.
2) Left-side colon cancers: Occult bleeding, changes in bowel habits or cramping.
Metastasis: Regional LNs; Liver (MC); Lungs; Bone
Premalignant Conditions of GIT

Oral cavity: Leukoplakia; Erythroplakia; Lichen planus
Esophagus: Barrett esophagus
Stomach: Atrophic gastritis; Gastric adenoma
Colon: Inflammatory bowel disease; Colonic adenomas; Peutz-Jeghers syndrome; Juvenile
polyposis
Primary Malabsorption Syndromes

Causes: Celiac disease; Tropical sprue; Whipple disease; Collagenous sprue; Disaccharidase
deficiency
17. Liver and Gallbladder
10 Marks
1) A 43 year old male, chronic alcoholic dies after a bout of profuse hematemesis. (Jan. 2011)
b) Describe the morphological changes in the target organ involved.
c) Write the sequential events that have led to death.
Ans: Cirrhosis of liver
2) A 50 year old chronic alcoholic was admitted with distended abdomen and hematemesis.
He appears emaciated and has altered sensorium. (May, 2006)
b) What is the gross and microscopic picture of the involved organ?
c) Mention the complications.
3) A 50 year old chronic alcoholic developed ascites with history of repeated bouts of
hematemesis and bleeding from rectum, admitted with coma and died. Scan showed shrunken
liver and splenomegaly. (April/May, 2004)
b) Mention the reasons in support of your diagnosis.
c) Describe the pathology of liver and spleen.
4 Marks
1) Morphology of acute viral hepatitis and its complications. (July, 2017)

2) Morphology of liver in alcoholic cirrhosis. (Feb. 2017)
3) Morphology of hepatocellular carcinoma. (July, 2016)
4) Chronic active hepatitis – Etiology, microscopic picture and fate. (Jan. 2016)
5) Etiopathogenesis of hepatocellular carcinoma. (Jan. 2015)
6) Etiopathogenesis and morphology of alcoholic liver disease. (July/Aug. 2014)
7) Etiologic and morphologic classification of cirrhosis of liver. (Jan. 2013)
8) Morphology of alcoholic cirrhosis. (Aug. 2010)
9) Pathogenesis of hepatocellular carcinoma. (March, 2010)
10) Liver abscesses. (May, 2006)
11) Alcoholic cirrhosis. (Sep. 2003)
2 Marks
1) Types of gall stones. (July, 2016)

2) Four causes for cirrhosis of liver. (July, 2015)
3) Types of gall stones and their complications. (July/Aug. 2014)
4) Four major etiologic factors associated with hepatocellular carcinoma. (Jan. 2014)
5) Gall stones-Types and complications. (July, 2012)
6) Alcoholic cirrhosis. (July, 2011)
7) Microscopic picture of alcoholic cirrhosis. (Aug. 2009)
8) Gall stones. (Feb. 2009)
9) Pigment gall stones. (March/April, 2008)
10) Serologic markers of hepatitis B virus (HBV). (Sep/Oct. 2007)
11) Etiology of hepatocellular carcinoma. (May, 2007)
12) Complications of cirrhosis. (Oct. 2005)
13) Etiology of hepatocellular carcinoma. (March/April, 2005)
14) Effects of gall stones. (Oct. 2004)
15) Hepatoma. (Oct/Nov. 2002)
16) Gall stones. (Oct/Nov. 2002)
Cirrhosis
Etiology: Chronic hepatitis B, Chronic hepatitis C, non-alcoholic fatty liver disease,
alcoholic liver disease
Pathogenesis:
1) Loss of hepatocytes with injury either by necrosis or apoptosis
2) Restoration of lost parenchyma is by regeneration, proliferation of residual cells or by stem
cell activation & differentiation to hepatocytes
3) Scarring is seen with fibrosis mediated by myofibroblasts derived from stellate cells.
PDGF, TGF-beta, IL-1 & TNF are involved.
4) Vascular derangement is seen as vascular shunting due to smooth muscle contraction of
blood vessels, contraction of myofibroblasts & compression of sinusoids.
Morphology: Gross Surface is seen with nodules of varying size.
Morphologic classification:
1) Micronodular cirrhosis: Nodules are of <3mm in diameter.
2) Macronodular cirrhosis: Nodules are of >3mm in diameter..
3) Mixed cirrhosis: Both micronodular & macronodular patterns are seen.
C/S – Gray-brown nodules are separated from one another by gray-white fibrous sepata.
Micro. Regenerative parenchymal nodules surrounded by fibrous bands & variable degrees
of vascular shunting.
2) Non-specific manifestations such as, anorexia, weight loss, & weakness.
3) Jaundice with pruritus, encephalopathy & coagulopathy
4) Palmar erythema & spider angiomas of skin in males
5) Hypogonadism & gynecomastia in males
Comp.:
1) Portal hypertension with clinical consequences
i) Ascites
ii) Portosystemic shunts manifesting as hemorrhoids, esophagogastric varices & caput
medusae
iii) Congestive splenomegaly with hypersplenism may cause pancytopenia.
iv) Hepatic encephalopathy
2) Hepatocellular carcinoma
Causes of death: Hepatic encephalopathy, bleeding from esophageal varices, bacterial
infections & hepatocellular carcinoma.
Viral Hepatitis
I) Acute viral hepatitis
It is the MC consequence of all hepatotropic viruses.

Causes: HAV, HBV, HCV, HDV, HEV
Phases:
1) Incubation period: Asymptomatic period
2) Pre-icteric phase: Seen with fatigue, anorexia, nausea, vomiting, or headache. Serum
transaminases may be elevated.
3) Icteric phase: Seen with jaundice, pruritus, tender hepatomegaly, dark-colored urine.
Elevated levels of serum bilirubin, transaminases & alkaline phosphatase seen.
4) Post-icteric phase: Clinical & biochemical recovery is seen.
Morphology
Gross Liver appears normal or slightly mottled with mild disease. Shrinkage of liver may be
seen with severe cases.
Micro 1) Most parenchymal injury is seen scattered throughout the hepatic lobule as spotty
necrosis or lobular hepatitis.
2) Lymphoplasmacytic infiltrate is seen.
3) Portal inflammation is minimal or absent.
4) Severe cases show confluent necrosis of hepatocytes around central veins leading to
central-portal bridging necrosis & parenchymal collapse.
Diagnosis: 1) HAV: Detection of serum IgM antibodies
2) HBV: Detection of HBsAg or antibody to HBcAg; PCR for HBV DNA
3) HCV: Anti-HCV antibodies; PCR for HCV RNA
4) HDV: Detection of IgM & IgG antibodies; HDV RNA in serum
5) HEV: Detection of IgM & IgG antibodies; PCR for HEV RNA
Fate: Recovery; Fulminant hepatitis
II) Chronic viral hepatitis
Def.: “Symptomatic, biochemical or serologic evidence of continuing or relapsing hepatic

disease for more than 6 months.”
Causes: HBV; HCV(MC); HDV
Morphology
1) Mononuclear portal infiltration is seen with interface hepatitis at the interface between
hepatocellular parenchyma & portal tract stroma.
2) Ground glass hepatocytes are seen with chronic hepatitis B.
3) Lymphoid aggregates are seen with chronic hepatitis C.
4) Fibrous septa may be seen extending between portal tracts along with increasing ductular
reaction leading to development of cirrhosis with scarring & nodule formation.
C/P: Fatigue, loss of appetite or mild jaundice; Mild tender hepatomegaly or splenomegaly.
Inv.: Elevated serum transaminases; Prolonged PT; Hyperglobulinemia; Hyperbilirubinemia;
Elevated alkaline phosphatase.
Diagnosis: 1) HBV: Detection of HBsAg or antibody to HBcAg; PCR for HBV DNA
2) HCV: Anti-HCV antibodies; PCR for HCV RNA
3) HDV: Detection of IgM & IgG antibodies; HDV RNA in serum
Comp.: Cirrhosis; Hepatocellular carcinoma
Liver Abscess
Site: Right lobe of liver (MC)
Cause: Bacteria (MC) (e.g., E.coli, Klebsiella, Pseudomonas)
Risk factors: Old age; Immunosuppression (AIDS); Chemotherapy
Routes of spread:
1) Hematogenous spread
2) Ascending infection in biliary tract
3) Direct infection
4) Iatrogenic
Morphology: Gross Hepatomegaly with single or multiple abscesses of varying size.
Micro. Abscesses are seen with pus containing liquefactive necrosis and dead neutrophils.
Reparative mechanisms are seen in the surrounding area.
C/P: Pain in the right upper quadrant, fever, tender hepatomegaly & jaundice may be seen.
Inv.: Leukocytosis; Elevated serum alkaline phosphatase; Blood culture

Comp.: Peritonitis
Alcoholic Liver Disease

“The threshold for the development of alcoholic liver disease is consumption of 80 gm/day of
alcohol.”
Sex: M>F
Risk factors: Female gender; Comorbid conditions (iron overload or viral hepatitis).
Pathogenesis: Exposure to alcohol causes steatosis, dysfunction of mitochondrial and
cellular membranes, hypoxia, and oxidative stress.
Forms of alcoholic liver injury:
I) Hepatic steatosis (Fatty liver): Reversible
Morphology: Gross Enlarged liver, soft, yellow & greasy
Micro: Micro & macrovesicular fatty change of hepatocytes
C/P: Hepatomegaly
Inv.: Mild elevation of serum bilirubin & alkaline phosphatase
II) Alcoholic steatohepatitis:

Morphology: Swelling of hepatocytes with Mallory-Denk bodies (eosinophilic cytoplasmic
inclusions made up of tangled skeins of intermediate filaments); Necrosis of hepatocytes with
surrounding neutrophilic infiltrates
C/P: Tender hepatomegaly, anorexia, weight loss, upper abdominal discomfort
Inv.: Elevated bilirubin , alkaline phosphatase, & aminotransferases (AST>ALT);
Neutrophilia
III) Alcoholic steatofibrosis:

Morphology: Fibrosis with chicken wire fence pattern around hepatocytes. Cirrhosis with
nodularity (Micronodular or Laennec cirrhosis)
Inv.: Elevated bilirubin, aminotransferases & alkaline phosphatase; Hypoproteinemia
Causes of death: Hepatic coma; GIT hemorrhage; Hepatorenal syndrome; Hepatocellular

carcinoma
Hepatocellular Carcinoma (Hepatoma)

“Primary malignant tumor of liver.”
Sex: M>F
Etiology: 1) Viral infections - HBV & HCV
2) Toxins - Alcohol & Aflatoxin;
3) Metabolic diseases - Hereditary hemochromatosis, Alpha 1 antitrypsin deficiency
Precursor lesions: Hepatocellular adenoma, High grade dysplastic nodule, Small cell
change.
Genetic alterations: Activating beta-catenin mutations & inactivating p53 mutations.
Morphology: Gross Hepatomegaly with unifocal large mass or multifocal nodules or
diffusely infiltrative lesion with pale or variegated appearance.
Micro: Well differentiated to anaplastic lesions.
C/P: Vague upper abdominal pain, fatigue, weight loss, or an abdominal mass. Jaundice,
fever, or esophageal variceal bleeding may be seen.
Inv.: Elevated serum alpha fetoprotein levels; Radiological (USG; CT; MRI).
Causes of death: Cachexia; GIT or esophageal variceal bleeding; Hepatic coma
Metastasis: Lungs
Cholelithiasis (Gall Stones)

“MC biliary tract disease.”
Types: Cholesterol stones & Pigment stones.
I) Cholesterol stones: MC in western nations.
Composition: Predominantly of cholesterol monohydrate crystals.
Risk factors: Advancing age, female sex, obesity, metabolic syndrome; estrogen exposure,
gall bladder stasis, hereditary factors.
Pathogenesis:
1) Cholesterol concentrations exceed the solubilizing capacity of bile (supersaturation)
2) Nucleation of cholesterol into solid monohydrate crystals, favoured by hypomotility of GB
3) Hypersecretion of mucus in the GB traps nucleated crystals & facilitates stone formation.
Morphology:
1) Pure cholesterol stones: Pale yellow, hard, single (ovoid) or multiple (faceted).
2) Gray-white to black discoloration is seen with calcium carbonate & bilirubin.
II) Pigment stones: MC in non- western nations.

Composition: Predominantly of calcium salts of unconjugated bilirubin.
Causes: Chronic hemolytic anemias; Severe ileal dysfunction; Biliary tract infections (E.coli,
Ascaris lumbricoides, C. sinensis).
Pathogenesis: Increased unconjugated bilirubin favors precipitation of calcium bilirubin
salts.
Morphology: They appear brown to black.
Black stones: Multiple, friable stones with spiculated contours, formed in sterile bile.
Brown stones: Single or few with soft, greasy consistency, seen with biliary tract infections.
C/P: Asymptomatic (MC); Right upper-quadrant or epigastric pain may be seen.

Comp.: Cholecystitis; Empyema; Cholangitis; Obstructive cholestasis; Pancreatitis;
Carcinoma of gall bladder; Gall stone ileus (Bouveret syndrome).
18. The Pancreas
10 Marks
1) A 48 years old male was admitted with acute abdominal pain following a heavy meal. He
is an alcoholic. (Oct. 2005)
b) What important investigations will support your diagnosis?
c) What is the pathology in the organ involved?
Ans: Acute pancreatitis
4 Marks
1) Acute pancreatitis. (Oct. 2008)

2) Acute pancreatitis. (Sep/Oct. 2007)
3) Acute pancreatitis. (Sep. 2003)
Acute Pancreatitis
“Reversible pancreatic parenchymal injury associated with inflammation”
Etiology: Alcoholism, gall stones, hypercalcemia, trauma, shock, mumps, medications
(azathioprine), hereditary pancreatitis (mutations in trypsinogen gene (PRSS1)).
Pathogenesis:
I) Mechanisms of inappropriate activation of pancreatic enzymes:
1) Pancreatic duct obstruction causes inflammation and interstitial edema, leading to
ischemic injury to acinar cells.
2) Primary acinar cell injury causes release of digestive enzymes & inflammation leading to
autodigestion of pancreas mediated by oxidative stress & increased calcium flux.
II) Consequences of inappropriate intrapancreatic activation of trypsin:
1) Activation of prophospholipase & proelastase, which degrade fat cells & damage elastic
fibres of blood vessels, respectively.
2) Activation of kinin, clotting & complement systems cause inflammation & small-vessel
thromboses leading to acinar damage.
Morphology: 1) Acute interstitial pancreatitis (Mild form):
Gross Enlarged pancreas
Micro. Mild inflammation, interstitial edema, & foci of fat necrosis.
2) Acute necrotizing pancreatitis (Severe form):
Gross Pancreas appears red-black with yellowish –white foci.
Micro. Parenchymal necrosis with hemorrhage & fat necrosis.
3) Hemorrhagic pancreatitis (Most severe form): Extensive parenchymal necrosis with
severe hemorrhage.
C/P: Abdominal pain; Anorexia, nausea & vomiting.
Inv.: Elevated serum levels of amylase & lipase, leukocytosis, hypocalcemia; CT scan.
Comp.: ARDS; ARF; Shock; Pancreatic pseudocyst.
19. The Kidney
10 Marks
1) A 60 year old male having fever and weight loss presented with painless hematuria, flank
pain and palpable mass in the left renal angle. CT scan confirmed a specific organ mass
lesion, regional lymph nodes and renal vein involvement. Chest radiography showed
pulmonary “cannonball” secondaries and his PCV is of 60%. (Jan. 2013)

b) Discuss the etiopathogenesis of the lesion.
c) Describe its morphology.
d) Mention various paraneoplastic syndromes produced by this lesion.
Ans: Renal cell carcinoma
2) A 40 year old female patient presented with clinical manifestations of massive proteinuria,
hypoalbuminemia, generalised edema with hyperlipidemia and lipiduria. (Aug. 2009)

b) Mention the causes of this syndrome.
c) Discuss the pathophysiology of the same.
Ans: Nephrotic syndrome
3) A 8 year old boy was admitted with malaise, fever, oliguria, cocoa-coloured urine 2 weeks
after recovery from sore throat. On examination, he was found to have peri orbital oedema
and moderate hypertension. (March/April, 2008)

b) Describe the etiopathogenesis of the condition?
c) What is the morphology of the organ involved?
d) List the urinary findings of the condition?
Ans: Post-streptococcal glomerulonephritis

4 Marks
1) Give the gross and microscopic findings in a case of chronic pyelonephritis. (July, 2017)
2) Morphology of renal cell carcinoma. (July, 2016)
3) Kidney lesions in hypertension. (Jan. 2016)
4) Etiopathogenesis of chronic pyelonephritis. (Jan. 2015)
5) Name the types of renal lesions in diabetic nephropathy and describe the histology of
glomerular lesions. (Jan. 2014)
6) Wilms tumor. (July, 2013)
7) Renal cell carcinoma. (July, 2012)
8) Chronic pyelonephritis. (July, 2011)
9) Renal dysplasia. (Jan. 2011)
10) Chronic contracted granular kidney. (March, 2010)
11) Chronic pyelonephritis. (Feb. 2009)
12) Kidney changes in hypertension. (Sep/Oct. 2007)
13) Chronic pyelonephritis. (May, 2007)
14) Wilms tumour. (May, 2006 )
15) Gross and microscopic picture of chronic pyelonephritis. (May, 2006 )
16) Diabetic kidney. (Oct. 2005)
17) Renal changes in diabetes mellitus. (Oct. 2004)
18) Classification of glomerular diseases. (Oct/Nov. 2002)
2 Marks
1) List four causes of chronic glomerulonephritis. (Feb. 2017)

2) Give the gross and morphologic picture of proliferative glomerulonephritis. (Jan. 2016)
3) Morphology of post streptococcal glomerulonephritis. (July/Aug. 2014)
4) Gross pathology of kidneys in benign and malignant nephrosclerosis. (Jan. 2012)
5) Renal stones. (April, 2009)
6) Wilms tumor. (Oct. 2008)
7) Wilms tumor. (March/April, 2005)
8) Stag horn calculus. (Oct. 2004)
9) Renal stones. (Sep. 2003)
10) Differences between adult and infantile polycystic diseases of the kidney. (March/April,
2003)
Glomerular Diseases – Classification

1) Primary glomerular diseases
Minimal-change disease
Acute postinfectious glomerulonephritis
Focal segmental glomerulosclerosis
Membranous nephropathy
Membranous glomerulonephritis
2) Glomerulopathies secondary to systemic diseases
Lupus nephritis
Diabetic nephropathy
Amyloidosis
Goodpasture syndrome
3) Hereditary disorders
Alport syndrome
Fabry disease
Acute Proliferative (Post-Streptococcal) Glomerulonephritis

It is characterized by formation of immune complexes with enlarged, hypercellular glomeruli
& development of nephritic syndrome.
Age: Children (6-10yrs)
Causative agent: Group A beta haemolytic streptococcus (types 1,4, & 12)
Pathogenesis: With pharyngeal or cutaneous streptococcal infection, antibodies formed
against streptococcal antigens (SpeB), form immune complexes in glomeruli. Inflammation
ensues with compliment activation leading to nephritic syndrome.
Morphology:
Light microscopy: Glomeruli show obliteration of capillary lumen because of infiltration
with neutrophils & monocytes and proliferation of endothelial & mesangial cells.
Interstitium shows edema & inflammation with RBC casts in tubules.
Immunofluorescence: Granular deposits of IgG & C3 in the mesangium & along the
glomerular basement membrane.
Electron microscopy: Discrete, amorphous electron-dense deposits are seen, mostly
subepithelial (hump-like) in location.
C/P: Features of acute nephritic syndrome (hematuria-smoky or colored urine, oliguria,
hypertension, azotemia) with fever, nausea & periorbital edema.
Inv.: 1) Urine: Mild proteinuria, hematuria (dysmorphic RBCs), red cell casts.
2) Antistreptococcal antibody (Anti-streptolysin O) titres are elevated.
3) Decreased serum complement (C3) levels
Comp.: RPGN; Chronic glomerulonephritis
Nephrotic Syndrome
Features: Massive proteinuria (3.5gm/day or more); Hypoalbuminemia (<3gm/dl);
Generalized edema; Hyperlipidemia & lipiduria
Etiology:
I) Primary glomerular disease: Minimal change disease; membranous nephropathy; FSGN;
MPGN
II) Systemic diseases: Diabetes mellitus; Amyloidosis; SLE; Infections ( Hepatitis B & C)
Pathogenesis:
I) Edema: Increased permeability of glomerular capillary wall for protein causes massive
proteinuria leading to hypoalbuminemia. Decreased plasma oncotic pressure causes
development of edema (generalised & pitting)
II) Hyperlipidemia: Increased blood cholesterol, TGs, VLDL &LDL levels seen because of
increased synthesis by liver, decreased catabolism of lipids or abnormal transport of lipids
leads to lipiduria.
III) Infections: Loss of immunoglobulins in urine increases the risk of developing
staphylococcal & pneumococcal infections
IV) Thrombotic complications: Loss of endogenous anticoagulants in urine causes
increased risk for thrombotic complications.
Chronic Glomerulonephritis
It represents end-stage glomerular disease.
Etiology: Membranous nephropathy; MPGN; IgA nephropathy; FSGN
Morphology: Gross Symmetrically contracted kidneys with diffuse granular surface; C/S
shows thinned cortex with increase in peripelvic fat.
Micro: Obliterated glomeruli form acellular eosinophilic masses; Interstitium shows tubular
atrophy with mononuclear cell infiltration & fibrosis; Arteriolar sclerosis
C/P: Anorexia, anemia, vomiting; Hypertension, proteinuria or azotemia
Comp.: Renal insufficiency or death
Diabetic Nephropathy
It is the MC cause of chronic kidney failure.
Renal failure is the 2nd MC cause of death in diabetics.
Morphology:
I) Glomerular lesions:
1) Diffuse basement membrane thickening of glomerular capillaries.
2) Diffuse increase in mesangial matrix causes diffuse mesangial sclerosis.
3) Nodular glomerulosclerosis or Kimmelstiel-Wilson disease:
i) Ovoid or spherical, often laminated nodules of matrix seen situated in the periphery of the
glomerulus. They are PAS-positive lying within the mesangial core of the glomerular lobules.
ii) Prominent accumulations of hyaline material is seen in capillary loops (fibrin caps) or
adherent to Bowmen capsules (capsular drops).
iii) Enlarging nodules may compress and engulf capillaries, obliterating the glomerular tuft.
iv) Tubular atrophy and interstitial fibrosis follows renal ischemia.
II) Renal vascular lesions: Macrovascular disease manifests as renal atherosclerosis and
hyaline arteriolosclerosis affecting both afferent & efferent arterioles.
III) Pyelonephritis: Seen either in acute or chronic form with inflammation of interstitium &
tubules. Acute pyelonephritis may cause necrotizing papillitis (papillary necrosis).
C/P: Microalbuminuria (earliest manifestation), overt nephropathy with macroalbuminuria,
often accompanied by hypertension, and end-stage renal disease.
Chronic Pyelonephritis
“Chronic inflammation affecting the tubules, Interstitium & renal pelvis.”
Predisposing factors: Vesicoureteral reflux & urinary tract obstruction
Etiology: Urinary tract infections (E.coli (MC), Proteus, Klebsiella, Enterobacter)
Forms
I) Reflux nephropathy: MC form, either U/L or B/L
Age: Childhood
Cause: Congenital vesicoureteral reflex & intrarenal reflex with superimposed infection.
II) Chronic obstructive pyelonephritis:
Cause: Diffuse or localized obstructive lesions, superimposed with infections.
Morphology: Gross
1) Irregularly scarred kidneys with asymmetrical involvement in B/L cases.
2) Coarse, discrete, corticomedullary scars overlying dilated, blunted or deformed calyces are
seen with flattening of the papillae.
3) Scarring usually involves poles of kidneys.
Micro. 1) Tubules are either atrophic or hypertrophic. Dilated tubules may be filled with
casts resembling colloid (thyroidisation).
2) Chronic interstitial inflammation & fibrosis are seen in the cortex & medulla.
C/P: Acute episodes present with back pain, fever, pyuria, & bacteriuria. Chronic disease
presents with renal insufficiency & hypertension.
Nephrosclerosis
Def.: Sclerosis of small renal arteries & arterioles with a strong association of hypertension
Risk factors: Advancing age; Diabetes mellitus; Hypertension
Pathogenesis:
1) Luminal narrowing caused by medial & intimal thickening and hyalinization of vascular
walls leads to ischemia.
2) Ischemia result in glomerulosclerosis & chronic tubulointerstitial injury.
Morphology:
Gross: Kidneys are either normal or reduced in size. Cortical surfaces may exhibit fine,
leathery granularity.
Micro
1) Hyaline arteriolosclerosis: Thickening & hyalinization of the walls of arterioles and small
arteries.
2) Fibroelastic hyperplasia: Medial hypertrophy, replication of the internal elastic lamina, and
increased myofibroblastic tissue in the intima of interlobular and arcuate arteries.
3) Patchy ischemia atrophy: Consists of foci of tubular atrophy & interstitial fibrosis and
glomerular alterations such as sclerotic glomeruli.
C/P: Mild proteinuria and rarely renal failure.
Malignant Nephrosclerosis
“A renal vascular disorder associated with malignant or accelerated hypertension.”
Risk factors: Preexisting benign essential hypertension, chronic renal disease or scleroderma
Pathogenesis: Luminal narrowing leading to ischemia is caused by 2 mechanisms
1) Vascular injury results in fibrinoid necrosis of vascular walls & intravascular thrombosis.
2) Hyperplasia of intimal smooth muscle of vessels cause hyperplastic arteriolosclerosis.
Morphology: Gross Flea-bitten appearance of the kidney with small, pinpoint petechial
hemorrhages on cortical surface.
Micro.
1) Fibrinoid necrosis of arterioles and small arteries: Seen as smudgy eosinophilic appearance
of vessel walls.
2) Hyperplastic arteriolosclerosis: Seen as concentric, laminated (onion-skin) intimal
thickening of interlobular arteries & arterioles.
C/P: Marked proteinuria, hematuria & renal failure
Autosomal Dominant (Adult) Polycystic Kidney Disease

Mode of inheritance: Autosomal dominant
It is usually bilateral
Genetic alterations: Mutations involving PKD1 & PKD2 which encode polycystin-1 &
polycystin-2 respectively.
Morphology: Gross Enlargement of kidneys with diffuse cystic external surface.
Micro. Cysts are seen filled with serous or red to brown fluid with dispersed normal
nephrons in between.
C/P: Asymptomatic; Abdominal pain, hematuria or renal colic may be seen; Polyuria or
hypertension can be associated.
Associations: Polycystic liver disease; Berry aneurysms; Mitral valve prolapse
Autosomal Recessive (Childhood) Polycystic Kidney Disease

Subcategories: Perinatal, neonatal, infantine & juvenile
Mode of inheritance: Autosomal recessive
Genetic alterations: Mutations of the PKHD1 gene, which encodes fibrocystin.
Morphology: Gross Enlarged kidneys with smooth external surface. C/S Spongy with many
cysts involving cortex & medulla.
Micro. Cylindrical dilation of all collecting tubules, lined with cuboidal epithelium.
C/P: Renal failure
Association: Congenital hepatic fibrosis in infantile & juvenile forms.
Adult Vs Childhood Polycystic Kidney Disease

Feature Adult Childhood
Inheritance AD AR
Age Adults Perinatal to Juvenile
Mutated gene PKD1 & PKD 2 PKHD 1
Defective protein Polycystin 1& 2 Fibrocystin
Surface of kidneys Cystic surface Smooth surface
Origin of cysts Tubules Collecting ducts
Liver comp. Polycystic liver disease Congenital hepatic fibrosis
Multicystic Renal Dysplasia

“A sporadic disorder, either unilateral or bilateral.”
Morphology: Gross Enlarged irregular & multicystic kidney
Micro. Cysts are lined by flattened epithelium. Islands of undifferentiated mesenchyme,
often with cartilage & immature collecting ducts are seen.
Associations: Ureteropelvic obstruction; Ureteral agenesis or atresia
Comp.: Renal failure in B/L cases.
Urolithiasis (Renal Calculi)

Site: Kidney (MC)
Sex: M>F
Age: 20-30yrs
Mostly unilateral & multiple
Predisposing factors: Increased concentration of stone constituents, changes in urinary pH,
decreased urine volume, presence of bacteria, deficiency in inhibitors of crystal formation.
Classification
I) Calcium stone: MC
Composition: Calcium oxalate or calcium oxalate mixed with calcium phosphate
Causes: Idiopathic hypercalciuria (MC); Hypercalciuria & hypercalcemia seen with
hyperparathyroidism, sarcoidosis.
II) Magnesium ammonium phosphate stones or triple stones or struvite stones
Causes: Infections with urea-splitting bacteria (proteus), causing alkaline urine.
e.g., Staghorn calculi
III) Uric acid stones
Causes: Hyperuricemia, with gout or leukemia; Acidic urine
IV) Cystine stones
Cause: Genetic defects in the renal reabsorption of cysteine; Acidic urine
Morphology: Stones may have smooth or spiculated surface.
Staghorn calculi: Massive stones with branching structures, occupying large portions of the
renal pelvis. They are usually composed of magnesium ammonium phosphate.
C/P: Asymptomatic; May cause renal colic, abdominal pain or hematuria.
Comp.: Secondary infections with urinary tract obstruction.
Renal Cell Carcinoma

“Primary malignant tumor of kidney.”
Age: 60-70yrs
Sex: M>F
Site: Poles of kidney (MC)
Risk factors: Tobacco usage (major); obesity; hypertension; unopposed estrogen therapy;
asbestos exposure; chronic kidney disease.
Etiology: Sporadic (MC) or familial. Familial forms are autosomal dominant such as, Von
Hippel-Lindau syndrome & hereditary papillary carcinoma.
Classification
I) Clear cell carcinoma: MC form
Genetic alterations: 3p deletions
Origin: Proximal tubular epithelium
Morphology: Gross Solitary unilateral spherical bright yellow-gray-white mass with areas of
hemorrhage & necrosis.
Micro. Most are well differentiated. Round or polygonal shaped cells with abundant clear or
granular cytoplasm in solid, trabecular or tubular patterns.
II) Papillary carcinoma

Genetic alterations: Trisomies 7 & 17 and loss of Y Chr. in males
Origin: Distal convoluted tubules
Morphology: Gross Large masses with hemorrhagic & cystic areas.
Micro. Cuboidal or low columnar cells are arranged in papillae with interstitial foam cells in
the cores. Scant, highly vascularized stroma is seen.
III) Chromophobe carcinoma:

Cell of origin: Intercalated cells of collecting ducts
Morphology: Pale eosinophilic ells, often with a perinuclear halo, arranged in solid sheets
IV) Collecting duct (Bellini duct) carcinoma:

Cell of origin: Collecting duct cells in the medulla
Morphology: Irregular channels are seen lined by highly atypical epithelium
C/P: Non-specific: Fever, weakness, & weight loss.

Specific: Costovertebral pain, palpable mass, & hematuria
Paraneoplastic syndromes: Polycythemia, hypercalcemia, hypertension, Cushing syndrome
Metastasis: Lungs (MC); Bones
Wilms Tumor
“Primary malignant tumor of kidney.” MC primary renal tumor of childhood.
Age: 2-5yrs
Mostly unilateral
Precursor: Nephrogenic rests
Etiology: Sporadic or familial.
Familial cases are seen with malformation syndromes such as WAGR syndrome; Denys-
Drash syndrome; Beckwith-Wiedemann syndrome.
Genetic alterations: Germline mutations of WT1 or WT2 genes.
Morphology: Gross Large, solitary well circumscribed mass. C/S: Soft, homogeneous, tan to
gray with occasional foci of necrosis & hemorrhage.
Micro. Triphasic elements:
1) Blastemal component shows sheets of small blue cells
2) Epithelial component is seen in the form of abortive tubules or glomeruli.
3) Stromal component is fibrocytic or myxoid in nature.
C/P: Large abdominal mass is felt. Hematuria, intestinal obstruction or hypertension may be
associated.
Metastasis: Lungs
20. The Lower Urinary Tract and Male Genital

System
10 Marks
1) 30 years old man with the H/o painless swelling in the right side of the scrotum for the past
6 months duration. Discuss about the differential diagnosis. (March/April, 2003)
4 Marks
1) Morphology of seminoma testis. (Feb. 2017)

2) Etiopathogenesis and morphology of carcinoma prostate. (July/Aug. 2014)
3) Undescended testes. (July, 2012)
4) Seminoma. (July, 2011)
5) Benign prostatic hyperplasia. (Sep/Oct. 2007)
2 Marks
1) Classification of germ cell tumors of testis. (Jan. 2015)

2) Name three (3) pre-malignant (carcinoma-in-situ) lesions of penis. Mention the common
infective agent associated with these lesions. (Jan. 2014)
3) Microscopic picture in seminoma. (July, 2013)
4) Name one benign tumor and three premalignant (carcinoma in situ) lesions of penis. (Jan.
2013)
5) Condyloma acuminata. (Aug. 2010)
6) Name the benign and malignant tumors of the penis. (March, 2010)
7) Seminoma testis. (Oct. 2005)
8) Classification of germ cell tumors of testis. (April/May, 2004)
Tumors of the Penis

Benign: Condyloma acuminatum
Malignant:
A) Carcinoma in Situ: Erythroplasia of Queyrat; Bowen disease; Bowenoid papulosis.
B) Invasive Carcinoma: Squamous cell carcinoma.
** Causative agent: HPV type 16
Condyloma Acuminatum
“Benign tumor of penis.” A sexually transmitted wart.
Cause: HPV types 6 & 11
Site: Penis (About coronal sulcus & inner surface of prepuce) or perineal areas.
Morphology: Gross Single or multiple, sessile or pedunculated, red papillary excrescences.
Micro. Papillary connective tissue stroma covered by epithelium with features of
hyperkeratosis, acanthosis & koilocytosis.
Comp.: Rare transformation to in situ or invasive cancers.
Cryptorchidism (Undescended Testes)

Congenital anomaly of testis.
“Complete or partial failure of the intra-abdominal testes to descend into the scrotal sac.”
Mostly unilateral & occurs as an isolated anomaly.
Site of arrest: Inguinal canal (MC)
Morphology: Gross Small, firm testis.
Micro Seminiferous tubules appear as dense cords of hyaline connective tissue outlined by
prominent basement membranes. Leydig cells appear prominent; Interstitial stroma is
increased.
C/P: Asymptomatic; Empty scrotal sac; Sterility.
Comp.: Inguinal hernia; Testicular cancer.
Testicular Tumors – Classification

A) Germ Cell Tumors
1) Seminomatous tumors: Seminoma; Spermatocytic tumor.
2) Nonseminomatous tumors: Embryonal carcinoma; Yolk sac tumor; Teratoma.
B) Sex Cord-Stromal Tumors: Leydig cell tumor; Sertoli cell tumor.
Seminoma
“Malignant tumor of testis.” MC germ cell tumor of testis.
Age: 30s
Precursor: Intratubular germ cell neoplasia (ITGCN)
Predisposing condition: Cryptorchidism
Genetic alterations: Isochromosome 12p
Morphology: Gross Enlargement of testis. C/S: Homogeneous, gray-white & lobulated.
Micro 1) Poorly demarcated lobules show sheets of uniform cells, which are large and round
to polyhedral & has a distinct cell membrane with clear cytoplasm and a large central nucleus
with prominent nucleoli.
2) Intervening fibrous septa shows lymphocytic infiltrate.
3) Anaplastic seminomas show frequent tumor giant cells & greater mitotic activity.
C/P: Painless enlargement of testis.
Metastasis: Lymphatic spread involving retroperitoneal para-aortic nodes. Hematogenous
dissemination occurs late to lungs.
Prognosis: Seminoma is radiosensitive & has best prognosis.
Painless Scrotal Mass

Differential diagnosis:
1) Common: Hydrocele; Nonincarcerated inguinal hernia; Varicocele
2) Uncommon: Spermatocele; Hematocele; Fluid overload; Testicular cancers (seminoma,
teratoma, lymphoma, Leydig cell tumor)
Benign Prostatic Hyperplasia (BPH) or Nodular hyperplasia

“MC benign prostatic disease in males aged >50yrs.”
Site: Transition zone of prostate
Risk factor: Advancing age
Etiopathogenesis: Dihydroxytestosterone (DHT) produced by stromal cells causes release of
growth factors (FGF & TGF beta) leading to increased proliferation of stromal cells &
decreased death of epithelial cells .
Morphology: Nodular hyperplasia of stromal & epithelial cells, form discrete nodules.
Early nodules (pale grey & firm) contain mostly fibromuscular stroma.
Late nodules (yellow-pink & soft) contain mostly glands.
Micro. Aggregations of bilayered (inner-columnar & outer-flattened) glands. Foci of reactive
squamous metaplasia in some cases.
C/P: Increased urinary frequency, nocturia, dysuria, difficulty in starting & stopping the
stream of urine; Distended bladder; Increased risk for urinary tract infection.
Carcinoma of the Prostate (Adenocarcinoma)

“MC cancer of males.”
Age: >50yrs
Site: Posterior aspect of peripheral zone
Etiopathogenesis:
1) Advancing age
2) Hormonal influences: Androgens play a role
3) Racial factors: Blacks are frequently affected
4) Environmental factors: Dietary influences play a role
5) Geographic factors: Uncommon in Asians.
6) Family history: Risk increased with the no. of first degree relatives with prostate cancer.
Genetic alterations: 1) Germ line mutations involving genes, such as BRCA2 & HOXB13
2) Acquired mutations such as, overexpression of the gene ETS, amplification of the gene
MYC, deletions involving the genes PTEN, & RB and loss of TP53
Precursor: Prostatic intraepithelial neoplasia (PIN)
Morphology: Gross Gritty & firm growth

Micro. Well differentiated tumors show uniform round crowded glands, lined by a single
layer of cuboidal or low columnar epithelium. Cytoplasm is pale-clear & nuclei are large with
large nucleoli. Poorly differentiated tumors show tumor cells infiltrating the stroma in the
form of cords, sheets & nests.
C/P: Asymptomatic; Nodule felt on rectal exam.; Late urinary symptoms (difficulty in
starting or stopping the stream, frequency, dysuria or hematuria).
Inv.: Elevated PSA levels; Elevated urine PCA3 scores; Digital rectal exam; Transrectal
USG; Transrectal needle biopsy.
Grading: Gleason system grades prostate cancer from grade 1 (well differentiated) to grade 5
(no glandular differentiation). Gleason score is obtained by adding primary grade assigned to
the dominant pattern with secondary grade given to the second most frequent pattern of the
tumor.
Metastasis: Bone (osteoblastic secondaries)
21. The Female Genital Tract
10 Marks
1) A 54-year old woman noted a 6-month history of progressive vaginal discharge sometimes
blood tinged. She was 2 years post menopausal and earlier took oral contraceptives for 10
years. She complains of right back pain and right leg swelling. The per-speculum
examination showed an unhealthy cervix with ulceration. (July/Aug. 2014)
a) What is the most likely diagnosis?

b) Write two (2) high risk, two (2) low risk microorganism & two (2) social factors
associated with this lesion.
c) Name the screening tests performed for it.
d) Describe the preventive measures.
Ans: Carcinoma cervix
2) A 40 year old female has 16 weeks amenorrhoea and on examination her uterus size was
larger and corresponds to 21 weeks size gestation. She complaints bleeding and passing grape
like vesicles per vaginum. Her blood and urine hCG levels are elevated and higher than
normal pregnancy. (July, 2013)

b) Mention the two types of this benign non-invasive lesion and discuss their different
pathogenesis.
c) Describe the gross and microscopic picture.
d) Mention the complications.
Ans: Hydatidiform mole
3) A 55 year old female presented with post menopausal bleeding and foul swelling vaginal
discharge. P/V examination revealed unhealthy, indurated and ulcerated cervix. (July, 2012)

b) How do you establish the diagnosis?
c) Describe the microscopic picture of the lesion.
4) 35 year old female has 12 weeks amenorrhoea. She is married 1 year ago. On examination
uterus size was larger and corresponding to 20 weeks gestation. She complaints of passing
grape like vesicles. Her blood and urine hCG levels are elevated than normal pregnancy.
(Oct. 2008)

b) Describe gross and microscopic picture of the lesion?
c) Discuss its complications.
Ans: Hydatidiform mole
5) A 55 years old female presented with bleeding per vaginum and white discharge. P/V
examination revealed unhealthy indurated and ulcerated cervix. (March/April, 2005)

b) What laboratory test will confirm the diagnosis?
c) What is the histopathology of the disease?
4 Marks
1) Etiology of carcinoma cervix. (July, 2016)

2) What are the pathogenic factors of endometrial cancer? Classify gonadal stromal tumours
of ovary and give the hormone secreted by each. (Jan. 2016)
3) Benign cystic teratoma of the ovary. (July, 2015)
4) Endometriosis – Definition, chief locations and histogenesis. (Jan. 2014)
5) Cervical intraepithelial neoplasia. (Jan. 2012)
6) Dermoid cyst-ovary. (Aug. 2010)
7) Brenner tumor. (March, 2010)
8) Choriocarcinoma. (April, 2009)
9) Dysgerminoma. (Feb. 2009)
10) Carcinoma cervix. (March/April, 2008)
11) Morphology of hydatidiform mole. (May, 2007)
12) Functioning ovarian tumours. (May, 2006)
13) Endometrial hyperplasia. (Oct. 2004)
2 Marks
1) Classify ovarian tumors. (July, 2017)

2) Give the names of four malignant ovarian tumours. (July, 2016)
3) What are the pathogenic factors of endometrial cancer. (Jan. 2016)
4) Classify gonadal stromal tumours of ovary and give the hormone secreted by each. (Jan.
2016)
5) Morphology of uterine leiomyoma. (Jan. 2015)
6) Name 4 surface epithelial tumors of ovary. (Jan. 2013)
7) Hydatidiform mole. (July, 2011)
8) Adenomyosis. (Jan. 2011)
9) Endometriosis. (Aug. 2010)
10) Endometriosis. (Aug. 2009)
11) Carcinoma in situ. (Feb. 2009)
12) Morphology of hydatidiform mole. (May, 2007)
13) Cervical carcinoma-in-situ. (May, 2006 )
14) Cervical intra-epithelial neoplasm (CIN). (Oct. 2005)
15) Etiology of carcinoma cervix. (April/May, 2004).
16) Choriocarcinoma. (Sep. 2003)
17) Dermoid cyst of the ovary. (March/April, 2003)
18) Classification of ovarian tumours. (Oct/Nov. 2002)
Cervical Carcinoma
Risk factors: Early age at first intercourse; Multiple sexual partners; Male partner with
multiple previous sexual partners; Persistent infection by high-risk strains of HPV.
Causative agent: HPV
High-risk HPVs: Types 16 (MC) & 18
Low-risk HPVs: Types 6 & 11
Cervical Intraepithelial Neoplasia (CIN) or Squamous Intraepithelial

Lesions (SIL)
Classification
1) Low –grade squamous intraepithelial lesion (LSIL) or CIN I: More common
Some may progress to HSIL but not directly to invasive carcinoma. Majority regress
spontaneously. Not a premalignant lesion.
2) High-grade squamous intraepithelial lesion (HSIL) or CIN II & III: Less common
Majority arise from LSIL. High risk of progression to invasive carcinoma. Considered as a
premalignant lesion.
Morphology: 1) LSIL - Immature cells are localized to lower third of epithelium.
2) HSIL - Immature cells expand to involve upper 2/3rds of the epithelial thickness.
3) Immature squamous cells show koilocytic atypia – Nuclear alterations with an associated
perinuclear halo.
4) Nuclear alterations: Nuclear enlargement, hyperchromasia, coarse chromatin granules, &
variation in nuclear size & shape.
Invasive Cervical Carcinoma
Age: 45yrs
Histologic subtypes: Squamous cell carcinoma (MC); Adenocarcinoma (2nd MC);
Adenosquamous & neuroendocrine carcinoma
Cause: High-risk HPVs (HPV-16 (MC) & HPV-18)
Morphology: Gross Fungating or infiltrative mass
Micro. 1) Squamous cell carcinoma: Nests & tongues of malignant squamous epithelium,
either keratinizing or nonkeratinizing, invading underlying cervical stroma.
2) Adenocarcinoma: Proliferation of glandular epithelium composed of malignant
endocervical cells with large, hyperchromatic nuclei & relatively mucin depleted cytoplasm.
C/P: Abnormal bleeding P/V
Spread: Local - Urinary bladder, ureters, rectum & vagina
Distant - Liver, lungs & bone marrow
Inv.: Pap test; Colposcopy; Biopsy
Comp.: Ureteral obstruction, pyelonephritis & uremia
Preventive measures: 1) Screening: With Pap test & HPV DNA testing
2) Colposcopy guided biopsy of abnormal mucosa
3) Vaccination against high-risk oncogenic HPVs
Endometriosis
“Presence of ectopic endometrial tissue at a site outside of the uterus.”
Age: 30 – 40s
Sites: Ovaries (MC), uterine ligaments, rectovaginal septum, cul de sac.
Theories that propose the origin of endometriotic lesions:
1) The regurgitation theory: It proposes that endometrial tissue implants at ectopic sites via
retrograde flow of menstrual endometrium.
2) The benign metastases theory: It states that benign endometrial tissue can spread to
distant sites (lung, brain) from uterus via blood vessels & lymphatic channels.
3) The metaplastic theory: It states that endometrium arises directly from coelomic
epithelium.
4) The extrauterine stem/progenitor cell theory: It proposes that stem/progenitor cells
from the bone marrow differentiate into endometrial tissue.
Pathogenesis: Overproduction of prostaglandins & estrogen enhances the survival and
persistence of endometriotic foci.
Morphology: Gross Formation of red-blue to yellow-brown nodules with bleeding. Fibrous
adhesions between tubes, ovaries, & others obliterate pouch of Douglas.
Micro. Endometrial glands & stroma with or without the presence of hemosiderin.
Chocolate cysts or endometriomas: Distorted ovary with large cystic masses filled with
brown fluid.
C/P: Severe dysmenorrhea, dyspareunia & pelvic pain; Menstrual irregularities; Infertility
Associations: Ovarian endometrioid & clear cell carcinomas
Adenomyosis
“Presence of endometrial tissue within the myometrium.”
Morphology: Gross Small foci of cystic hemorrhagic areas
Micro. Irregular nests of endometrial stroma with or without glands within the myometrium ,
separated from the basalis by at least 2-3mm
C/P: Irregular & heavy menses; colicky dysmenorrhoea, dyspareunia & pelvic pain
Association: Endometriosis
Endometrial Hyperplasia
“An increased proliferation of the endometrial glands relative to the stroma, with prolonged
estrogenic stimulation of the endometrium.”
Etiology: Obesity; Menopause; PCOD; Functioning granulosa cell tumors of the ovary;
Estrogen replacement therapy
Genetic alterations: Mutations in PTEN gene that increase PI3K / AKT signaling.
WHO Classification: Non-atypical hyperplasia & atypical hyperplasia
Morphology: 1) Non-atypical hyperplasia: Increase in the gland to stroma ratio with glands
showing variation in size & shape.
2) Atypical hyperplasia (Endometrial intraepithelial neoplasia): Proliferative glands
arranged back to back with complex outlines & nuclear atypia. Individual cells appear round,
with features of nuclei having open chromatin & conspicuous nucleoli.
C/P: Abnormal bleeding P/V
Comp.: Atypical hyperplasia may progress to endometrial carcinoma
Carcinoma of the Endometrium

“MC invasive cancer of the female genital tract.”
Classification
1) Type I (endometrial) Carcinoma: Most common
Age: 55-65yrs
Precursor: Endometrial hyperplasia.
Risk factors: Obesity; Diabetes; Hypertension; Infertility; Unopposed estrogen stimulation
Genetic alterations: Mutations that increase PI3K / AKT signaling, such as mutations in the
PTEN gene, PIK3CA gene, KRAS gene or ARID1A
Morphology: Gross Localized polypoid mass or diffusely infiltrative tumor.
Micro. 1) Well differentiated or endometrioid carcinoma (grade 1): MC; Composed
almost entirely of well-formed glands with lack of intervening stroma.
2) Moderately differentiated (grade 2): Shows well-formed glands mixed with areas
composed of solid sheets of cells for 50% or less of the tumor.
3) Poorly differentiated (grade 3): Shows more than 50% solid growth pattern.
Spread: Via lymphatics
2) Type II (Serous) Carcinoma
Age: 65-75yrs
Precursor: Endometrial atrophy
Sub types: Serous carcinoma (MC); Clear cell carcinoma; Malignant mixed mullerian tumor
Serous carcinoma
Precursor: Serous endometrial intraepithelial carcinoma

Genetic alterations: Mutations in the TP53 gene
Morphology: Gross: Large bulky mass or deeply invasive into the myometrium
Micro. They are poorly differentiated (grade III) tumors
Papillary growth pattern, with cells exhibiting high N-C ratio, atypical mitotic figures,
hyperchromasia & prominent nucleoli.
Spread: Lymphatic or transtubal spread
C/P: Asymptomatic; Irregular or postmenopausal vaginal bleeding with excessive

leukorrhoea.
Inv.: Ultrasound; Biopsy
Leiomyoma (Fibroid)
“Benign smooth muscle cell tumor myometrium.”
Site: Myometrium of the corpus, often multiple
Genetic alterations: Mutations in the MED12 gene
Types: Intramural (within the myometrium); Sub mucosal (beneath the endometrium); Sub
serosal (beneath the serosa)
Morphology: Gross Circumscribed round, gray-white, discrete firm masses of varying size.
C/S: Whorled pattern of smooth muscle bundles.
Micro. 1) Bundles of smooth muscle cells with admixed fibrous connective tissue.
2) Tumor cells show oval nucleus & long, slender bipolar cytoplasmic processes.
C/P: Asymptomatic; Abnormal bleeding, urinary frequency & impaired fertility.
Comp.: Spontaneous abortion; Fetal malpresentation; Post-partum hemorrhage
Ovarian Tumors - Classification

1) Surface epithelial tumors:
Serous tumors (benign, borderline & malignant);
Mucinous tumors (benign, borderline & malignant);
Endometrioid tumors (benign, borderline & malignant);
Clear cell tumors (benign, borderline & malignant);
Transitional cell tumors (benign, borderline & malignant)
2) Sex cord-stromal tumors:
Granulosa cell tumors; Fibromas; Thecomas; Sertoli-Leydig cell tumors
3) Germ cell tumors: Teratoma; Dysgerminoma; Yolk sac tumor
4) Metastatic cancer
Functioning Ovarian Tumors

Sex cord-stromal tumors:
1) Estrogen producing tumors: Granulosa cell tumors; Thecomas
C/P: Precocious pseudopuberty in pediatric patients. Postmenopausal bleeding in
postmenopausal patients
2) Androgen producing tumors: Sertoli-Leydig cell tumors; Leydig cell tumors
C/P: Virilization
Transitional Cell Tumors or Brenner Tumors

Brenner tumors contain neoplastic epithelial cells, resembling urothelium.
Types: Benign (MC), borderline & malignant
Usually unilateral.
Benign Brenner tumor

Morphology: Gross Solid or cystic masses varying in size.
Micro. Fibrous stroma is seen with nests of epithelial cells resembling urothelium often with
mucinous glandes in their centre.
Mature (Benign) Teratoma (Dermoid Cyst)

“MC germ cell tumor of ovary.”
Age: Young women
Mostly unilateral.
Origin: From ovum after 1st meiotic division
Morphology: Gross 1) Unilocular cystic masses with hair & sebaceous material.
2) Cyst wall is thin, lined by gray-white, wrinkled epidermis with protruding hair shafts.
3) Tooth structures & area of calcification may be seen within the wall.
Micro.: 1) Cyst wall is lined with stratified squamous epithelium with underlying sebaceous
glands & hair shafts.
2) Cartilage, bone , thyroid & neural tissue may be found.
Comp.: Malignant transformation to squamous cell carcinoma (Rare)
Paraneoplastic syndrome: Inflammatory limbic encephalitis
Associations: Mucinous cystadenoma; Dysgerminoma
Dysgerminoma
“Malignant germ cell tumor of ovary.” Ovarian counterpart of testicular seminoma.
Mostly unilateral.
Age: 20-30s
Predisposing conditions: Gonadal dysgenesis
Morphology: Gross Solid yellow-white to gray-pink, soft & fleshy.
Micro. Large vesicular cells growing in sheets or cords separated by scant fibrous stroma.
Tumor cells have a clear cytoplasm, well-defined cell boundaries, & centrally placed regular
nuclei. Intervening stroma is infiltrated by mature lymphocytes.
Association: Benign cystic teratoma
Hydatidiform Mole
“Gestational trophoblastic disease, with proliferation of placental tissue.”
Age: Teenagers & 40-50yrs
Types: Complete mole & partial mole
A) Complete mole
1) Pathogenesis: Fertilization of an empty egg by a sperm with duplication of its genetic
material (androgenesis). Genetic material is completely of paternal origin.
2) Karyotype: Diploid (46XX)
3) Embryo not identified
4) Comp.: Risk of development of invasive mole & choriocarcinoma.
B) Partial mole
1) Pathogenesis: Fertilization of an egg with 2 sperms
2) Karyotype: Triploid (e.g., 69XXY)
3) Fetal tissues are present
4) Comp.: Risk of development of invasive mole but not choriocarcinoma.
Morphology: Gross Cystic, thin walled, translucent friable mass of grape like structures.
Micro: 1) Complete mole: All or most of the villi are enlarged (swollen edematous-
hydropic), scalloped in shape with central cavitation (cisterns). Entire villous circumference
shows extensive trophoblastic proliferation.
2) Partial mole: Only a fraction of villi are enlarged covered with focal & less marked
trophoblastic hyperplasia.
C/P: Spontaneous miscarriage
Inv.: Elevated HCG (complete>partial); Ultrasound
Choriocarcinoma
“Malignant tumor of trophoblastic cells.”
Predisposing conditions: Complete mole (MC); Previous abortions; Normal pregnancy;
Ectopic pregnancy
Morphology: Gross Soft, fleshy, yellow-white tumor with large areas of necrosis &
hemorrhage.
Micro: 1) Proliferating cytotrophoblasts & syncytiotrophoblasts without villi formation.
2) Abundant mitoses with some atypical forms.
C/P: Irregular vaginal spotting of a bloody, brown fluid
Inv.: Elevated HCG levels
Metastasis (Hematogenous): Lungs (MC), vagina
22. The Breast
10 Marks
1) A 20 year old female presented with a painless slowly growing freely mobile solitary lump
in the lower part of her left breast. On examination, the nipple is normal. The lump is not
fixed to the overlying skin. No axillary lymph nodes are palpable. (July, 2016)

b) Discuss various investigations to confirm your final diagnosis.
c) Describe the gross and microscopic picture of the lesion.
Ans: Fibroadenoma
2) A 45 year old lady presented with a painless swelling in the left breast for 3 months
duration. On examination the swelling was firm, fixed to the overlying skin. Left axillary
lymph nodes were enlarged. Fine needle aspiration of the swelling showed loosely cohesive
cells with pleomorphic hyperchromatic nuclei and prominent nucleoli. (July, 2015)

b) Describe the etiopathogenesis of this condition.
c) How will you classify this condition?
d) What are prognostic factors for this condition?
Ans: Carcinoma of the breast
3) 40 year old female presented with lump in the breast. The lump is hard and adhered to the
underlying structures and axillary lymph nodes are enlarged. (Aug. 2010)

b) How do you classify them?
c) Discuss the etiology and pathogenesis of the lesion.
Ans: Carcinoma of the breast
4) A 20 year old female presented with a painless slowly growing freely mobile solitary lump
in the lower part of her left breast. On examination the nipple is normal. The lump is not
fixed to the overlying skin. No axillary lymph nodes are palpable. (April, 2009)

b) Discuss various investigations to confirm your final diagnosis.
c) Describe the gross and microscopic picture of the lesion.
Ans: Fibroadenoma
4 Marks
1) Microscopic types of breast cancer. (Jan. 2016)

2) Medullary carcinoma breast. (Jan. 2011)
3) Cystosarcoma phyllodes. (Aug. 2009)
4) Prognostic factors of breast carcinoma. (May, 2007)
5) Classification of breast tumors. (Oct. 2005)
6) Histological types of breast carcinoma. (Apr/May, 2004)
2 Marks
1) Paget disease of nipple – Gross and microscopic picture. (Jan. 2014)

2) Diagrammatically illustrate the two microscopic patterns of fibroadenoma breast. (Jan.
2013)
3) Name the benign tumors of the breast. (July, 2012)
4) Paget disease of breast. (Jan. 2012)
5) Phyllodes tumor. (Feb. 2009)
6) Paget disease of breast. (Oct. 2008)
7) Fibroadenoma. (Oct. 2008)
8) Phyllodes tumor. (March/April, 2008)
9) Paget disease of the nipple. (Sep/Oct. 2007)
10) Fibrocystic disease of the breast. (March/April, 2003)
Nonproliferative Breast Changes (Fibrocystic Changes)

“Benign epithelial lesion of the breast, not associated with an increased risk of breast cancer.”
Morphology: 1) Cysts: They are lined by a flattened atrophic epithelium or metaplastic
apocrine cells. They contain turbid, brown or blue colored fluid (blue-dome cysts).
Calcifications are common.
2) Fibrosis: Chronic inflammation & fibrosis results with the release of cystic contents into
the stroma following their rupture.
2) Adenosis: Increased no. of acini per lobule are seen, lined by columnar cells.
C/P: Palpable nodularity is felt with fibrosis
Inv.: FNAC; Mammography; Ultrasound
Tumors of Breast - Classification

I) Epithelial tumors
Benign epithelial proliferations: Sclerosing Adenosis; Adenomas
Epithelial-myoepithelial tumors: Pleomorphic adenoma; Adenoid cystic carcinoma
Papillary lesions: Intraductal papilloma; Intraductal papillary carcinoma
Precursor lesions: Ductal carcinoma in situ; Lobular carcinoma in situ
Invasive breast carcinoma: Invasive ductal carcinoma; Invasive lobular carcinoma;
Carcinoma with medullary features; Mucinous carcinoma; Tubular carcinoma
II) Mesenchymal tumors: Lipoma; Myofibroblastoma; Angiosarcoma
III) Fibroepithelial tumors: Fibroadenoma; Phyllodes tumor
IV) Tumors of the nipple: Nipple adenoma; Paget disease of the nipple
V) Metastatic tumors
Benign Tumors of Breast

Fibroaednoma; Phyllodes tumor; Adenoma; Intraductal papilloma; Pleomorphic adenoma
Carcinoma of the Breast

“MC non-skin malignancy of women.” 2nd MC cause cancer deaths in women.
Site: Upper outer quadrant (1st MC); Central portion (2nd MC).
Cell of origin: Cells in the terminal duct lobular unit
Mostly unilateral.
Risk factors: Advancing age (MC: 70-80yrs); Female gender; First-degree relatives with
breast cancer; Early menarche; Nulliparity; Absence of breast feeding; Older age at 1st
pregnancy; Radiation to the chest; Postmenopausal obesity; Postmenopausal hormone
replacement; Mammographic density; Alcohol consumption.
Etiology: Sporadic, related to hormonal exposures with de novo mutations or familial with
germ line mutations.
Genetic alterations: Loss of function mutations involving tumor suppressor genes having a
role in DNA repair & maintenance of genomic integrity.
BRCA1 & BRCA2 – MC; TP53 &CHEK2: Rare
Classification
A. Noninvasive: Ductal carcinoma in situ; Lobular carcinoma in situ
B. Invasive: Invasive ductal carcinoma; Invasive lobular carcinoma; Carcinoma with
medullary features; Mucinous carcinoma; Tubular carcinoma
Carcinoma in situ: Neoplastic proliferation of epithelial cells that is confined to ducts &
lobules by the basement membrane.
I) Ductal carcinoma in situ
Morphology: Gross Vague nodularity
Micro. i) Comedo DCIS: Tumor cells with pleomorphic high-grade nuclei & areas of central
necrosis.
ii) Noncomedo DCIS: Cribriform or solid or micropapillary patterns are seen. No high-grade
nuclei or central necrosis are seen.
II) Lobular carcinoma in situ
Morphology: Uniform population of round discohesive cells are seen with oval or round
nuclei having small nucleoli involving ducts & lobules. Mucin-positive signet ring cells are
seen.
Invasive ductal carcinoma: Tumor has penetrated through the basement membrane and
grows within stroma.
Molecular subtypes
I) ER-positive, HER2-negative: MC
1) MC subtype with germline mutations in BRCA2
2) Precursors: Flat epithelial atypia, atypical ductal hyperplasia
3) Genetic alterations: Gains of chr.1q, losses of chr.16q & activating mutations in PIK3CA
II) HER2-postive
1) MC subtype with germline mutations in TP53
2) Precursor: Atypical apocrine adenosis
3) Genetic alterations: Amplification of the HER2 gene
4) Either ER-positive or ER-negative
III) ER-negative, HER2-negative

MC subtype with germline mutations in BRCA1
Morphology
Gross Hard, irregular mass, may be seen with retraction of nipple or dimpling of the skin.
Micro. Almost all are adenocarcinomas
1) ER-positive, HER2-negative carcinoma: Well to poorly differentiated
2) HER2-positive carcinoma: Majority are poorly differentiated
3) ER-negative, HER2-negative carcinoma: Almost all are poorly differentiated
Histologic grade: Nottingham Histologic Score
1) Grade I (well differentiated): Tubule formation with small round nuclei & low
proliferative rate.
2) Grade II (moderately differentiated): Some tubule formation with solid clusters or single
infiltrating cells. More nuclear pleomorphism & proliferative rate is seen.
3) Grade III (poorly differentiated): Invade as ragged nests or solid sheets of cells with
enlarged irregular nuclei. High proliferative rate & tumor necrosis are seen
Spread: Local: Regional lymph nodes; Distant: Bone (MC), viscera or brain
Special histologic types
1) Lobular carcinoma
Genetic alteration: Biallelic loss of expression of CDH1
Morphology Gross Hard irregular mass
Micro. Discohesive infiltrating tumor cells, often showing signet ring morphology with
absence of tubule formation.
Metastasis: Peritoneum & retroperitoneum, leptomeninges, GIT, ovaries & uterus
2) Mucinous (colloid) carcinoma:
Morphology Gross Soft or rubbery
Micro. Clusters & small islands of tumor cells within large lakes of mucin.
3) Tubular carcinoma: Well-formed tubules are seen with apocrine snouts
4) Papillary carcinoma: Tumor cells lining fronds of fibrovascular tissue form papillae.
5) Medullary Carcinoma: It is a ER-negative, HER2-negative tumor.
Genetic alterations: Many show reduced BRCA1 expression.
Morphology: Gross Well-circumscribed soft mass
Micro. i) Solid, syncytium-like sheets of large cells with pleomorphic nuclei, and prominent
nucleoli.
ii) Frequent mitotic figures.
iii) Moderate to marked lymphoplasmacytic infiltrate surrounding & within the tumor
iv) A pushing (noninfiltrative) border
v) Minimal desmoplasia
vi) DCIS is minimal or absent
Prognostic and Predictive Factors

I) Related to the extent of carcinoma
1) Tumor size: Increased size of primary tumor carries poor prognosis
2) Invasive carcinoma versus carcinoma in situ: Carcinoma in situ carries excellent
prognosis
3) Lymph node metastases: Absence of axillary LN involvement carries good prognosis.
4) Distant metastases: Carry poor prognosis
5) Lymphovascular invasion: Carry poor prognosis
6) Inflammatory carcinoma: Carry poor prognosis
5) Locally advanced disease: Involvement of skin or skeletal muscle carries poor prognosis
II) Related to tumor biology

1) Molecular subtype: Based on proliferation and ER & HER2 expression
2) Special histologic types: Metaplastic carcinoma or micropapillary carcinoma carry poor
prognosis
3) Histologic grade: Based on Nottingham Histologic Score
4) Proliferation rate: Carcinomas with higher proliferation rates carry poor prognosis
5) Estrogen & progesterone receptors:
6) HER2: Overexpression of HER2 is seen with poor prognosis
Paget Disease of the Nipple

Rare manifestation of breast cancer.
Morphology: Gross Unilateral erythematous scaly lesion
Micro 1) Malignant cells (Paget cells) are seen in the nipple skin extending from DCIS.
2) Underlying invasive poorly differentiated carcinoma may be seen.
C/P: Pruritus; Palpable mass
Inv.: Biopsy; Cytology of exudate
Fibroadenoma
“Benign stromal tumor of breast.” MC benign tumor of female breast.
Frequently bilateral & multiple.
Age: 20 – 30yrs
Origin: Intralobular stroma
Risk factor: Use of cyclosporine A
Morphology: Gross Well circumscribed, rubbery, grayish white nodules of varying size.
C/S: Slitlike spaces.
Micro. 1) Stroma – often myxoid
2) Epithelium may be surrounded by stroma (pericanalicular pattern) or compressed &
distorted by it (intracanalicular pattern).
C/P: Firm, freely mobile, discrete mass is felt on palpation.
Inv.: Biopsy; FNAC; Mammography; Ultrasound
Comp.: Infarction & inflammation during pregnancy
Phyllodes Tumor (Cystosarcoma Phyllodes)

Origin: Intralobular stroma
Age: 60s
Genetic alterations: Gains in chromosome 1q.
Morphology: Gross Round to oval mass of varying size with bosselated surface.
C/S: Gray-white with cystic cavities and areas of hemorrhage & necrosis.
Micro. 1) The stroma frequently overgrows the epithelial component, creating bulbous
protrusions covered by epithelium.
2) They have higher cellularity, higher mitotic rate, nuclear pleomorphism & infiltrative
borders.
C/P: Palpable breast mass
Inv.: Ultrasound; Mammography; FNAC; Biopsy
Comp.: Recurrence - Occasional with low-grade tumors, but often with intermediate & high
grade tumors. Hematogenous dissemination may be seen with high-grade tumors.
23. The Endocrine System
4 Marks
1) Hashimoto thyroiditis. (July, 2013)

2) Pathology of Graves disease. (Jan. 2013)
3) Medullary carcinoma thyroid. (Jan. 2012)
5) Morphology of pheochromocytoma. (March, 2010)
6) Hashimoto thyroiditis. (April, 2009)
7) Complications of diabetes mellitus. (Feb. 2009)
8) Medullary carcinoma of thyroid. (Feb. 2009)
9) Pheochromocytoma. (Oct. 2008)
10) Pheochromocytoma. (Sep/Oct. 2007)
11) Graves disease. (May, 2007)
12) Thyroid adenoma. (Oct. 2004)
13) Hashimoto thyroiditis. (March/April, 2003)
14) Toxic goiter. (Oct/Nov. 2002)
2 Marks

2) Name four malignant tumors of thyroid. (Feb. 2017)
3) Microscopic appearance of papillary carcinoma of thyroid. (July, 2016)
4) Microscopic patterns of follicular adenoma thyroid. (Jan. 2016)
5) Name four malignant tumours of the thyroid. (July, 2015)
6) Three causes of primary hyperparathyroidism and one cause of secondary
hyperparathyroidism. (Jan. 2015)
7) Microscopic picture of thyroid in Graves disease. (Jan. 2014)
8) Follicular adenoma thyroid – Gross and histological picture. (July, 2012)
9) Four clinical features of primary hyperparathyroidism. (Jan. 2011)
10) Morphology of Hashimoto thyroiditis. (May, 2006)
11) Hashimoto thyroiditis. (May, 2006)
12) Pheochromocytoma. (May, 2006)
13) Pathogenesis of Graves disease. (April/May, 2004)
14) Papillary carcinoma of thyroid. (Sep. 2003)
Hashimoto Thyroiditis
“Autoimmune thyroid disease.” MC cause of hypothyroidism in iodine sufficient world.
Age: 45-65 yrs
Sex: F>M
Genetic alterations: Polymorphisms in immune function genes, CTLA4 & PTPN22.
Pathogenesis: 1) Breakdown in self-tolerance to thyroid autoantigens with formation of
autoantibodies against thyroglobulin & thyroid peroxidase (TPO).
2) CD8+ cytotoxic T cells may destroy thyroid follicular cells.
3) Interferon-gamma mediated activation of macrophages may result in damage to follicles.
Morphology: Gross Diffuse symmetrical enlargement with intact capsule.
C/S: pale yellow-tan, firm
Micro 1) Follicles are atrophic and may be lined by Hurthle cells (epithelial cells with
abundant, eosinophilic granular cytoplasm).
2) Extensive mononuclear cell infiltrate with small lymphocytes & plasma cells.
3) Increased interstitial connective tissue.
C/P: 1) Painless goitre with hypothyroidism.
2) Hashitoxicosis-Transient thyrotoxicosis preceding hypothyroidism.
Inv.: TFT: Raised TSH; Low free T3, T4; Antibodies: Anti thyroglobulin & anti TPO
antibodies; Ultrasound; FNAC; Biopsy
Associations: SLE, Sjogren syndrome, Type 1 DM
Comp.: Extranodal marginal zone B-cell lymphoma
Graves Disease
“Autoimmune thyroid disorder.” MC cause of endogenous hyperthyroidism.
Age: 20-40yrs
Sex: F>M
Genetic alterations: Polymorphisms in immune function genes, CTLA4 & PTPN22.
Pathogenesis: Formation of autoantibodies against TSH receptor is seen.
1) Thyroid stimulating immunoglobulin (TSI) stimulates TSH receptor causing
hyperthyroidism - MC
2) TSH receptor blocking antibodies in some may cause hypothyroidism
Morphology: Gross Diffuse symmetric enlargement. C/S: Soft, meaty appearance.
Micro. 1) Hypertrophy & hyperplasia of follicular epithelial cells
2) Follicles lined by cells appearing tall & crowded, forming small papillae. Colloid appears
pale, with scalloped margins
3) Lymphoid aggregates are seen throughout the interstitium
C/P: Triad Hyperthyroidism; Infiltrative ophthalmopathy; Infiltrative dermopathy
1) Goitre with diffuse enlargement of thyroid
2) Thyrotoxicosis: Tachycardia, palpitations, anxiety
3) Sympathetic overactivity causes wide staring gaze & lid lag.
4) Ophthalmopathy with exophthalmos
5) Infiltrative dermopathy (Pretibial myxedema): Scaly thickening & induration of skin,
mostly overlying shins.
Inv.: 1) TFT: Elevated free T3 & T4 and low TSH levels.
2) Radioiodine scans: Diffusely increased uptake of iodine.
Associations: SLE; Addison disease; Type 1 diabetes
Primary Tumors of the Thyroid

Benign: Follicular adenoma
Malignant: Papillary carcinoma; Follicular carcinoma; Medullary carcinoma; Anaplastic
carcinoma
Follicular Adenoma
“Benign tumor of thyroid.”
Origin: Follicular epithelial cells
Genetic alterations: Somatic mutations of the TSH receptor signaling pathway are found in
toxic adenomas.
Morphology: Gross: 1) Solitary, spherical encapsulated gray-white to red-brown mass.
2) Areas of hemorrhage, fibrosis, calcification & cystic change are seen.
Micro: 1)Uniform appearing follicles that contain colloid are seen.
2) Occasionally, neoplastic cells exhibit oxyphil or Hurthle cell change.
3) Intact, well-formed capsule encircling the tumor is seen.
4) Various architectural patterns are observed such as solid/trabecular, microfollicular,
normofollicular or macrofollicular types.
C/P: Unilateral painless mass in the neck. Larger masses may cause dysphagia.
Inv.: Ultrasound, FNAC, Biopsy, Radionuclide scanning
Comp.: Thyrotoxicosis with toxic adenomas; Rare transformation to follicular carcinoma
Papillary Carcinoma
“MC Malignant tumor of thyroid.”
Origin: Follicular epithelial cells
Age: 25-50yrs
Risk factor: Ionizing radiation
Genetic alterations: Chromosomal rearrangements of the RET gene (RET/PTC
translocations) and gain of function mutations in BRAF gene.
Morphology: Gross Solitary or multifocal; Solid or cystic (MC); Circumscribed or
infiltrative. C/S: Areas of fibrosis, calcification or papillary foci.
Micro. 1) Papillae with fibrovascular stalks lined by well differentiated single or multi-
layered cuboidal epithelium.
2) Nuclear features: Ground glass or Orphan Annie eye nuclei - Optically clear or empty
appearance with finely dispersed chromatin; Intranuclear inclusions (pseudo-inclusions) or
intranuclear grooves with invaginations of the cytoplasm.
3) Psammoma bodies within the cores of papillae.
Variants: Follicular variant (MC); Tall cell variant; Diffuse sclerosing variant; Papillary
microcarcinoma.
C/P: Asymptomatic mass in the neck. Advanced cases present with hoarseness, dysphagia,
dyspnoea or cough.
Inv.: Ultrasound, FNAC, Biopsy, Radionuclide scanning
Metastasis: Cervical lymphnodes, lung
Medullary Carcinoma
“Malignant neuroendocrine tumor of thyroid.”
Origin: Parafollicular cells or C cells
Age: 1) Sporadic & familial medullary thyroid carcinoma (FMTC) – Adults (40-50s)
2) MEN 2A or MEN 2B associated – Young
Etiology: 1) Sporadic (MC) – Seen as a solitary nodule.
2) Familial: In association with MEN 2A, MEN 2B or as FMTC – Bilaterality &
multicentricity are common
Genetic alterations: Activating point mutations in RET proto-oncogene.
Morphology: Gross: Pale gray to tan, firm & infiltrative. Areas of necrosis & hemorrhage
are seen in larger masses.
Micro: Polygonal to spindle shaped cells forming nests, trabeculae or follicles. Acellular
amyloid deposits are present in the stroma. Multicentric C-cell hyperplasia in the surrounding
thyroid may be seen in familial cases.
C/P: 1) Sporadic: Mass in neck; Dysphagia or hoarseness
2) Familial: Associated features of MEN A, MEN 2B or FMTC
Inv.: Raised calcitonin; Raised CEA; In some, raised serotonin, ACTH & VIP
Paraneoplastic syndromes: Diarrhea; Cushing syndrome
Toxic Goitre
Causes: Graves disease; Toxic multinodular goitre; Toxic adenoma; Subacute thyroiditis
Hyperparathyroidism
“Hyperfunctioning of parathyroid gland with elevated PTH levels.”
Types: 1) Primary 2) Secondary 3) Tertiary
Primary Hyperparathyroidism
“An autonomous overproduction of PTH is seen.”
MC cause of asymptomatic hypercalcemia.
Causes: Adenoma (MC); Primary hyperplasia; Carcinoma
Age: Adults
Sex: F>M
Parathyroid adenoma
Etiology: Sporadic (MC) or Familial

Genetic alterations with sporadic adenomas:
1) Cyclin D1 gene inversions leading to overexpression of cyclin D1
2) Mutations involving MEN1 tumor suppressor gene
Familial parathyroid adenomas; They are seen with MEN-1 & MEN-2A, caused by
germline mutations of MEN1 & RET, respectively.
Morphology: Gross Solitary, well-circumscribed encapsulated tan to reddish-brown nodule.
Micro Mostly of uniform polygonal chief cells with few nests of larger oxyphil cells.
Adipose tissue is inconspicuous. A rim of compressed parathyroid tissue is visible at the edge
of adenoma separated by a fibrous capsule.
C/P: 1) Asymptomatic hyperparathyroidism: Symptom free stage.
2) Symptomatic primary hyperparathyroidism:
Bone: Osteoporosis & osteitis fibrosa cystica leading to fractures.
GIT: Constipation, nausea, peptic ulcers, & pancreatitis
Renal: Nephrolithiasis & chronic renal insufficiency
CNS: Depression, lethargy, & seizures
Neuromuscular: Weakness & fatigue
Cardiac: Aortic or mitral valve calcifications
Inv.: Elevated PTH levels, Hypercalcemia, hypophosphatemia, increased urinary excretion of
both calcium & phosphate.
Secondary Hyperparathyroidism
“Compensatory overactivity of the parathyroid glands due to chronic hypocalcemia.”

Causes: Renal failure (MC), inadequate intake of calcium, Vit.D deficiency, & steatorrhea.
Morphology: Gross Hyperplasia of parathyroid glands
Micro. Increased no. of chief cells or water-clear cells in a diffuse or multinodular
distribution. Fat cells are decreased in no. Metastatic calcification is seen involving many
tissues.
C/P: 1) Features of chronic renal failure 2) Milder skeletal abnormalities 3) Ischemic damage
to tissues (calciphylaxis)
Pheochromocytoma
“Tumor of adrenal medulla, secreting catecholamines.”
Origin: Chromaffin cells
Rule of 10s: 10% - Malignant; 10% - Bilateral; 10% - Extra adrenal;
10% - Non hypertensive
Etiology: Sporadic or familial (25%).
Genetic alterations: Some of the familial cases are associated with MEN-2A, and MEN-2B,
caused by germline mutations of RET.
Morphology: Gross Lobular tumors of variable size with remnants of the adrenal gland.
C/S: Small tumors - yellow-tan;
Large tumors– Areas of hemorrhage, necrosis or cystic change.
Micro Clusters of polygonal to spindle shaped chromaffin cells, surrounded by sustentacular
cells in small nests or alveoli (zellballen); Chief cells show fine granular cytoplasm & round
to ovoid nucleus with a stippled salt & pepper chromatin. Rich vascular network is seen.
C/P: Hypertension with paroxysmal episodes, associated with tachycardia, palpitations,
headache, sweating & tremors.
Comp.: Catecholamine cardiomyopathy with congestive heart failure, myocardial infarction
& ventricular fibrillation.
Inv.: Increased urinary excretion of free catecholamines & their metabolites
(vanillylmandelic acid, & metanephrins); Biopsy.
Metastasis (Malignant pheochromocytoma): Regional lymph nodes; Liver, lung & bone
Complications of Diabetes Mellitus

I) Acute metabolic complications
i) Hypoglycemia: Most common
C/P - Dizziness, sweating, confusion & palpitations. Loss of consciousness may occur.
ii) Diabetic ketoacidosis: Seen predominantly with type 1 diabetes.
C/P: Fatigue, nausea & vomiting, severe abdominal pain, fruity odor and deep, labored
breathing (Kussmaul breathing). Altered consciousness & coma may be seen.
Inv.: Ketonemia & ketonuria with hyperglycemia.
iii) Hyperosmolar hyperosmotic syndrome: Seen with type 2 diabetics.
C/P: Severe dehydration & impairment of mental status.
II) Chronic complications: They cause majority of the morbidity & mortality.
i) Diabetic macrovascular disease: MC causes of mortality in long standing diabetics.
Site: Large & medium-sized muscular arteries are involved.
C/P: Accelerated atherosclerosis with increased risk of myocardial infarction, gangrene of
the lower extremities and stroke.
ii) Diabetic microangiopathy:
Site: Small vessels are affected
a) Diabetic nephropathy: Leading cause of end-stage renal disease.
C/P: Microalbuminuria (earliest manifestation), overt nephropathy with macroalbuminuria &
end-stage renal disease.
b) Diabetic retinopathy:
C/P: Increased risk of developing cataracts & glaucoma. Visual impairment or total blindness
may be associated.
c) Diabetic neuropathy:
C/P: Distal symmetric polyneuropathy of the lower extremities affecting both sensory &
motor function, autonomic neuropathy with bowel or bladder dysfunction & diabetic
mononeuropathy with sudden footdrop or wristdrop.
iii) Increased susceptibility for infections: Skin infections, TB, pneumonia & pyelonephritis.
24. The Skin
4 Marks
1) Morphology of malignant melanoma. (Jan. 2015)

2) Malignant melanoma. (March/April, 2008)
2 Marks
1) Morphology of basal cell carcinoma. (July, 2016)

2) Microscopic picture of malignant melanoma. (Jan. 2012)
3) Name four preneoplastic lesions of skin. (Jan. 2011)
4) Histology of malignant melanoma. (Aug. 2010)
5) Name four variant forms of nevocellular nevi. (March, 2010)
6) Melanoma. (April, 2009)
7) Basal cell carcinoma. (Feb. 2009)
8) Pre malignant conditions of skin. (May, 2007)
9) Vesiculo-bullous lesions of skin. (May, 2006)
10) Rodent ulcer. (Oct. 2004)
Variant Forms of Melanocytic Nevi

Congenital nevus; Blue nevus; Spitz nevus; Halo nevus; Dysplastic nevus.
Melanoma
“Malignant tumor of skin.”
Sites: Skin (MC) – Upper back in men; Back & legs in women
Others: Esophagus; uvea; mucous surfaces of oral & anogenital tracts
Risk factors: Fair skin; Sun exposure (UV radiation)
Etiology: Sporadic (MC) or genetic
Pathogenesis: Ultraviolet radiation causes DNA damage
Genetic alterations: 1) Mutations of the gene CDKN2A
2) Activating mutations in BRAF
3) Mutations activating telomerase enzyme
Morphology: Gross 1) Asymmetrical with irregular & notched borders.
2) Increased diameter (>6mm) with variegated color.
Patterns of growth 1) Radial growth: Horizontal spread within the epidermis & superficial
dermis. No metastatic risk. Ex.: Superficial spreading melanoma (MC type), lentigo maligna
2) Vertical growth: Invasion into the deeper dermis is seen with appearance of a nodule.
Metastatic risk is associated.
Micro.: Melanoma cells are large with large nuclei having irregular contours, peripheral
chromatin clumping & red nucleoli.
C/P: Asymptomatic; Itching or pain may be seen.
Prognosis: Favourable prognosis is with female gender, thinner tumor depth (Breslow
thickness), no or very few mitoses, many tumor-infiltrating lymphocytes, absence of
regression, lack of ulceration, absent lymph node metastasis.
Metastasis: Regional lymph nodes
Pre-malignant Lesions of Skin

Actinic keratosis; Solar keratosis; Bowen disease; Leukoplakia; Xeroderma pigmentosum.
Basal Cell Carcinoma (Rodent Ulcer)

“Malignant tumor of skin.” MC invasive carcinoma
Locally aggressive, slow-growing & rarely metastasize.
Risk factors: Sun exposure; Old age; Fair skin; Xeroderma pigmentosum;
Immunosuppression.
Etiology: Sporadic or genetic
Genetic alterations: Loss of function mutations involving PTCH gene, that activate the
Hedgehog pathway signaling.
Morphology: Gross 1) Pearly papules with telangiectasias or ulceration
2) Local invasion of bone or facial sinuses in advanced cases.
Growth patterns 1) Multifocal lesions involving only epidermis
2) Nodular lesions involving dermis
Micro. 1) Cords & islands of basophilic cells with hyperchromatic nuclei, embedded in a
mucinous matrix, surrounded by lymphocytes & fibroblasts.
2) Cells exhibit palisading in the periphery of the tumor islands.
3) Stroma is seen retracting away from tumor creating separation artifacts.
Associations: Nevoid basal cell carcinoma syndrome or Gorlin syndrome
Blistering (Bullous) Diseases

1) Inflammatory Blistering Disorders: Pemphigus; Bullous pemphigoid, Dermatitis
herpetiformis.
2) Noninflammatory blistering disorders: Epidermolysis bullosa; Porphyria.
25. Bones, Joints, and Soft Tissue Tumors
4 Marks
1) Classify bone tumors. Give X-ray appearance and microscopic picture of giant cell tumor.
(July, 2017)
2) Morphology of osteoclastoma. (Feb. 2017)
3) Skeletal Ewing sarcoma – common sites, X-ray appearance and microscopic picture. (Jan.
2014)
4) Giant cell tumor – Bone. (July, 2013)
5) Morphology of common and classic osteosarcoma. (Jan. 2013)
6) Ewing sarcoma. (July, 2012)
7) Morphology of giant cell tumor of bone. (Jan. 2011)
8) Morphology of pyogenic osteomyelitis. (March, 2010)
9) Gouty arthritis. (April, 2009)
10) Giant cell tumor of bone. (Oct. 2008)
11) Ewing sarcoma. (May, 2007)
12) Osteosarcoma. (May, 2006)
13) Giant cell tumor of bone. (Osteoclastoma). (Oct. 2005)
14) Osteomyelitis. (March/April, 2005)
15) Giant cell tumor. (March/April, 2003)
2 Marks
1) Gross appearance of osteogenic sarcoma. (July, 2015)

2) Microscopic appearance of giant cell tumor of bone. (Jan. 2015)
3) Giant cell tumor – common sites and its radiological and microscopic picture. (July/Aug.
2014)
4) Four (4) conditions known to be associated with development of osteosarcoma. (Jan. 2012)
5) Osteoclastoma. (July, 2011)
6) Sequestrum. (Aug. 2010)
7) Osteitis fibrosa cystica. (Aug. 2009)
8) Tuberculous osteomyelitis. (March/April, 2008)
9) Gouty tophi. (May, 2006)
10) Gout. (May, 2006)
11) Tuberculous osteomyelitis. (Oct. 2004)
12) Ewing sarcoma. (April/May, 2004)
13) Osteosarcoma. (Sep. 2003)
14) Ewing sarcoma. (Oct/Nov. 2002)
Generalized Osteitis Fibrosa Cystica (von Recklinghausen disease

of bone)
“It represents the combination of increased osteoclast activity, peritrabecular fibrosis and
cystic brown tumors seen in association with severe primary hyperparathyroidism.”
Pathogenesis: Excessive or inappropriate levels of PTH cause unabated osteoclast activity
leading to skeletal changes.
Morphology:
1) Osteoporosis:
i) Decreased bone mass seen especially affecting phalanges, vertebrae, & proximal femur.
ii) In the medullary bone, osteoclasts dissect trabeculae centrally along the length causing
dissecting osteitis with an appearance of railroad tracks.
iii) The marrow spaces around the affected surfaces are replaced by fibrovascular tissue.
2) Brown tumor: Microfractures and secondary hemorrhages seen with an ingrowth of
reparative fibrous tissue forming a mass known as a brown tumor. Cystic degeneration may
be seen.
Osteomyelitis
“Inflammation of bone & marrow secondary to infection with bacteria (MC), virus, fungi or
parasites.”
Pyogenic Osteomyelitis
Cause: Bacteria -Staph.aureus (MC); H. influenza & Group B streptococci in neonates;

E.coli, Pseudomonas & Klebsiella with genitourinary tract infections or IVDA; Salmonella in
patients with sickle cell anemia.
Routes of spread: Hematogenous; Extension from a contagious site; Direct implantation
Risk factors: Children: Trivial mucosal injuries occurring during defecation or minor skin
injuries. Adults: Open fractures or surgical procedures.
Site: Neonates – Metaphysis, Epiphysis or both; Children – Metaphysis; Adult – Epiphysis &
subchondral region.
Morphology: 1) Acute phase: Neutrophilic infiltration; Necrosis of bone & marrow;
Formation of subperiosteal abscesses & sequestrum (dead bone); Draining sinus is seen with
formation of soft tissue abscess.
2) Chronic phase: Reactive bone deposition (involucrum) is seen around segment of dead
bone with ingrowth of fibrous tissue.
C/P: Severe localized pain, fever with chills.
Inv.: Leucocytosis; Blood culture, biopsy & bone cultures.
X-ray: Lytic lesion with surrounding sclerotic zone.
Comp.: Pathologic fracture; Secondary amyloidosis; Endocarditis; Squamous cell carcinoma
of the draining sinus tract.
Tuberculous osteomyelitis
“Osseous infection can be seen with pulmonary or extrapulmonary TB.”
Risk factor: Immunosuppression
Spread: Direct extension or hematogenous spread
Micro: Granulomas with caseous necrosis
C/P: Asymptomatic; Localized pain, low-grade fever with chills, & weight loss
Comp.: Pott disease (Tuberculous spondylitis); Tuberculous arthritis; Sinus tract formation;
psoas abscess; Amyloidosis
Bone Tumors – Classification

A) Cartilage forming:
Benign: Osteochondroma, Chondroma; Malignant: Chondrosarcoma
B) Bone forming:
Benign: Osteoid osteoma, Osteoblastoma; Malignant: Osteosarcoma
C) Unknown origin:
Benign: Giant cell tumor; Malignant: Ewing sarcoma
D) Metastatic tumors
Osteosarcoma
“Bone forming malignant tumor of bone.”
Age: <20 yrs (MC) & older adults
Sex: Men>Women
Predisposing conditions for secondary osteosarcoma in older adults: Paget disease; Bone
infarcts; Prior radiation; Chronic osteomyelitis
MC subtype: Primary, intramedullary, osteoblastic & high grade
Site: Metaphysis
Bones: Distal femur & proximal tibia.
Genetic alterations: Mutations involving genes such as RB, TP53, INK4a
Morphology: Gross Gritty, gray-white mass with areas of hemorrhage & cystic degeneration
Micro. Pleomorphic cells with large hyperchromatic nuclei; Tumor giant cells & atypical
mitotic figures; Formation of neoplastic bone with fine, lace-like architecture.
C/P: Painful enlarging mass; Pathological fracture may be seen.
X-ray: Mixed lytic & blastic mass with infiltrative margins; Reactive periosteal bone
formation; Codman triangle (Triangular shadow between the cortex & raised ends of
periosteum).
Metastasis: Lungs, bone & brain.
Ewing Sarcoma
“Malignant bone tumor of unknown origin.”
Age: <20 yrs
Sex: Boys>Girls
Site: Diaphysis
Bones: Femur, pelvic bones
Genetic alterations: (11:22) translocation
Morphology: Gross Soft, tan-white with areas of hemorrhage & necrosis.
Micro. Sheets of uniform small, primitive round cells without obvious differentiation with
scant clear cytoplasm; Stroma is little; Necrosis is prominent.
C/P: Painful enlarging mass with fever; Affected site is tender & swollen.
Inv.: Anemia, leukocytosis & raised ESR.
X-ray: Lytic tumor with infiltrative margins; Deposition of reactive bone in an onion-skin
fashion.
Giant Cell Tumor (Osteoclastoma)

Benign, but locally aggressive bone tumor
Age: 20-40 yrs
Site: Epiphysis
Bones: Distal femur & proximal tibia
Pathogenesis: Primitive osteoblast precursors cause proliferation & differentiation of
osteoclast precursors into mature osteoclasts, cause destructive resorption of bone matrix.
Morphology: Gross Solitary large red-brown mass with cystic degeneration
Micro. Sheets of uniform oval mononuclear cells & numerous osteoclast-type giant cells.
Nuclei of both cell types are ovoid with prominent nucleoli. Reactive bone may be present at
the periphery.
C/P: Bulging soft tissue mass is seen; Affected site is tender & swollen
X-ray: Lytic tumor with reactive bone formation
Comp.: Pathological fracture; Recurrence; Metastasis to lungs (Rare)
Gout
“Crystal-induced arthritis with monosodium urate (MSU) within & around joints.”
Types: 1) Primary (MC): Cause is unknown
2) Secondary: Known underlying cause
Age: >30yrs
Sex: M>F
Risk factors: Obesity, metabolic syndrome, alcoholism & renal failure.
Etiology: “Hyperuricemia is associated.”
1) Primary gout is seen with overproduction of uric acid for unknown reasons.
2) Secondary gout is seen with overproduction (leukemia) or reduced excretion (chronic renal
disease) or both (Lesch-Nyhan syndrome).
Pathogenesis: 1) Precipitation of MSU crystals into the joint trigger cytokine & complement
mediated recruitment of leukocytes. 2) Phagocytosis of crystals is followed by production of
IL-1, free radicals, proteases & prostaglandins causing tissue injury & inflammation.
Morphology: 1) Acute arthritis: i) Neutrophilic infiltrates are seen involving synovium &
synovial fluid with MSU crystals in their cytoplasm.
ii) Synovium is edematous & congested with small clusters of MSU crystals.
iii) MSU crystals are long, slender & needle shaped, and are negatively birefringent.
2) Chronic tophaceous arthritis: Crystals encrust the articular surface and form deposits in
synovium. Synovium becomes hyperplastic, fibrotic & forms a pannus that destroys the
underlying cartilage leading to juxta-articular bone erosions.
3) Tophi: Formed by large aggregates of MSU crystals surrounded by an inflammatory
reaction of foreign body giant cells. They are seen in articular cartilage, ligaments, tendons,
bursae or soft tissues.
4) Gouty nephropathy: Deposition of MSU crystals or tophi in the renal medullary
interstitium or tubules leading to uric acid nephrolithiasis & pyelonephritis.
C/P: 1) Asymptomatic hyperuricemia
2) Acute arthritis: Most 1st attacks are monoarticular (MC site – 1st metatarsophalangeal
joint). Later, insteps, ankles, heels, & knees are involved. Affected joint presents with severe
pain & erythema. 3) Asymptomatic intercritical period: Symptom free interval.
4) Chronic tophaceous arthritis: Juxta-articular bone erosion & loss of the joint space are
seen.
26. The Central Nervous System
4 Marks
1) CSF findings in pyogenic meningitis. (Feb. 2017)

2) CSF changes in meningitis. (July, 2016)
3) Meningioma. (July, 2015)
4) Morphology of meningioma. (July/Aug. 014)
5) Morphology of astrocytoma. (Jan. 2014)
6) Astrocytoma. (Jan. 2012)
7) Glioblastoma. (July, 2011)
8) Astrocytoma. (Jan. 2011)
9) Morphology of meningioma. (Aug. 2010)
10) Astrocytoma. (Aug. 2009)
11) Astrocytoma. (Oct. 2005)
12) Glioblastoma multiforme. (April/May, 2004)
13) Berry aneurysm. (Oct/Nov. 2002)
2 Marks
1) Name four brain tumors. (Jan. 2015)

2) CSF findings in pyogenic meningitis. (July, 2013)
3) Mention the site, size, appearance and common complication of Berry Aneurysm. (Jan.
2013)
4) Pyogenic meningitis – CSF findings. (July, 2012)
5) Various histological types of meningioma. (March, 2010)
6) Name four glial tumors. (April, 2009)
7) Brain abscess. (March/April, 2008)
8) Meningioma. (Sep/Oct. 2007)
9) Meningioma. (May, 2006)
10) Berry aneurysm. (Oct. 2005)
11) Berry aneurysm. (Oct. 2004)
12) Astrocytoma. (Sep. 2003)
Saccular Aneurysms (Berry Aneurysms)

“MC type of intracranial aneurysm.”
Site: Anterior circulation of circle of Willis, near major arterial branch points
Risk factors: Cigarette smoking & hypertension
Etiology: Sporadic (MC) or developmental
Pathogenesis: Underlying defect in the media of the vessel promotes aneurysm formation.
Associations: Autosomal dominant PCKD; Neurofibromatosis type 1; Marfan syndrome
Morphology: Gross 1) Single or multiple saccular, thin walled, bright red translucent
outpouchings of variable size (few mm to 2 or 3 cm in diameter) with neck & apex.
2) Atheromatous plaques, calcification, or thrombi are seen in the wall or lumen of aneurysm.
Micro: 1) Aneurysmal sac is made up of thick hyalinised intima & a covering of adventitia.
2) Absence of media & internal elastic lamina
Comp.: Rupture results in subarachnoid hemorrhage
Meningitis
Acute meningitis
“Meningitis is an inflammation of leptomeninges & CSF within the subarachnoid space.”
Etiology: Infections (MC)
Acute pyogenic (Bacterial) meningitis
Etiology:
Neonates: E.coli & group B streptococcus
Young adults: Neisseria meningitidis
Elderly: Streptococcus pneumoniae & Listeria monocytogenes
Morphology: Gross Exudate is seen within the leptomeninges over surface of the brain.
Meningeal vessels are engorged.
Micro. Neutrophils seen within subarachnoid space & around leptomeningeal blood vessels.
C/P: Headache, photophobia, neck stiffness, fever, irritability, & clouding of consciousness
Inv.: CSF Appears cloudy with increased no. of neutrophils, increased protein & low
glucose; Staining & culture of CSF.
Comp.: Cerebritis; Ventriculitis; Venous thrombosis; Hydrocephalus
Aseptic meningitis
Etiology: Viral (MC) – Enteroviruses

C/P: Headache, photophobia, neck stiffness, fever, irritability & altered consciousness
Inv.: CSF appears clear with increased no. of lymphocytes, increased protein & normal
glucose; Bacterial cultures are negative.
Chronic Meningitis
Etiology: Mycobacterium tuberculosis
C/P: Headache, mental confusion, & vomiting
Inv.: CSF appears cloudy with increased no. of mononuclear cells or a mixture of neutrophils
& mononuclear cells, an elevated protein & a moderately reduced or normal glucose.
Brain Abscess
“Localized focus of liquefactive necrosis of brain tissue with accompanying inflammation.”
Etiology: Bacteria – Streptococcus & staphylococcus (MC)
Routes of spread: Direct implantation, local extension from adjacent foci or hematogenous
spread.
Predisposing conditions: Acute bacterial endocarditis; Bronchiectasis; Immunosuppression
Morphology: Discrete lesions with central liquefactive necrosis, surrounded by exuberant
granulation tissue. Later, a surrounding collagenous capsule & a zone of reactive gliosis are
seen. Adjacent brain tissue shows edema.
C/P: Progressive focal neurologic deficits; Features of increased intracranial pressure
Inv.: CSF – Increased WBCs; Increased protein; Normal glucose
Comp.: Meningitis; Venous sinus thrombosis; Herniation of brain
Primary Tumors of Brain – Classification

1) Gliomas: Astrocytomas; Oligodendrogliomas; Ependymomas; Angiocentric glioma
2) Neuronal Tumors: Gangliogliomas; Central neurocytoma
3) Poorly differentiated tumors: Medulloblastoma
Astrocytoma
“Gliomas arising from progenitor cells.”
Types: Diffuse infiltrating or localized
I) Diffuse infiltrating Astrocytoma
Site: Cerebral hemisphere
Age: 40 – 60yrs
Types:
1) Diffuse astrocytoma: WHO grading - Grade II
Morphology: Gross Poorly defined, gray, infiltrative tumors of variable size.
C/S: Firm or soft & gelatinous with cystic degeneration
Micro. Increased cellular density with fibrillary background; Variable nuclear pleomorphism.
2) Anaplastic astrocytoma: WHO grading - Grade III
Micro: Greater cellular density & nuclear pleomorphism. Frequent mitoses are seen.
3) Glioblastoma (glioblastoma multiforme): WHO grading - Grade IV
Types:
i) Primary glioblastoma: MC form.
1) Occurs in older individuals as a new onset disease.
2) Genetic alterations: Mutations in the gene PTEN, deletions of chromosome 10, &
amplification of the EGFR oncogene.
ii) Secondary glioblastoma:
1) Occurs in younger individuals due to progression of a low-grade astrocytoma.
2) Genetic alterations: Mutations of TP53, & point mutations in IDH genes.
Morphology: Gross Alternating firm & white, soft & yellow areas with areas of hemorrhage
& cystic degeneration.
Micro. 1) Densely cellular tumor with prominent nuclear pleomorphism.
2) Necrosis of serpentine pattern in areas of hypercellularity.

3) Tumor cells show pseudo-palisading along the edges of necrosis.
4) Vascular cell proliferation produces tufts of cells, forming glomeruloid body.
C/P: Seizures, headache & focal neurologic deficits.
II) Localized Astrocytoma
Pilocytic astrocytoma
Slow growing & relatively benign localized astrocytoma.

Age: Children & young adults
Site: Cerebellum
Genetic alterations: Alterations in the BRAF signaling pathway are seen.
WHO grading: Grade I
Morphology: Gross Solid or cystic (MC) mass
Micro. 1) Biphasic tumor with both, loose microcystic & fibrillary areas
2) Bipolar cells with long, thin hairlike processes form dense fibrillary meshworks.
3) Rosenthal fibers & eosinophilic granular bodies are characteristic
4) Increased vascularity
Association: Neurofibromatosis type 1
Meningioma
“Benign tumor arising from meningothelial cells of arachnoid.”
Age: Adults
Sex: F>M
Sites: Parasagittal aspect of the brain convexity, dura over the lateral convexity, wing of
sphenoid, olfactory groove.
Risk factor: Radiation to head & neck
Genetic alterations: 1) Sporadic – Mutations of NF2 tumor suppressor gene on chr.22
2) Genetic - 22q deletion, including the loss of NF2 gene.
Morphology: Gross – Solitary, round dural based encapsulated masses with bosselated or
polypoid appearance.
Micro. WHO Grades I to IV
Grade I – Relatively low risk of recurrence or aggressive growth
1) Syncytial (meningothelial) meningioma with whorled clusters of cells in syncytial pattern.
2) Fibroblastic meningioma with elongated cell & abundant collagen deposition.
3) Transitional meningioma with features of syncytial & fibroblastic types.
4) Psammomatous meningioma with psammoma bodies
Grade II – Higher rate of recurrence & more aggressive local growth
Atypical meningiomas with atypical features (increased cellularity, small cells with a high N-
C ratio or necrosis) & increased no. of mitoses.
Grade III – Highly aggressive & high propensity to recur
1) Anaplastic (malignant) meningioma with pleomorphic cells showing high mitotic rates.
2) Papillary meningioma with pleomorphic cells arranged around fibrovascular cores.
C/P: Vague nonlocalizing symptoms or features of compression of underlying brain.
Association: Neurofibromatosis type 2
Miscellaneous
Diseases of White Blood Cells, Lymph Nodes, Spleen

and Thymus
4 Marks
1) Burkitt lymphoma. (Jan. 2014)

2) Reed-Sternberg (R-S) cell. (March/April, 2008)
3) Morphology of Hodgkin lymphoma. (Sep. 2003)
2 Marks
1) Staging of Hodgkin disease. (July, 2017)

2) Burkitt lymphoma. (July/Aug. 2014)
3) Hodgkin lymphoma – WHO classification. (July, 2013)
4) Reed-Sternberg giant cells. (July, 2011)
5) Variants of Reed-Sternberg cell. (Aug. 2009)
6) Causes of lymphadenopathy. (Sep/Oct. 2007)
7) Nodular sclerosis type of Hodgkin lymphoma. (May, 2007)
8) Microscopic picture of Hodgkin lymphoma. (March/April, 2005)
9) Reed-Sternberg cell. (April/May, 2004)
10) Hodgkin disease. (Oct/Nov. 2002)

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Undergraduate Pathology Series

High-Yield Exam Oriented Review for MBBS

Dr. Shiva M.D.

Dedicated to Dr. G. Taraka Rajaram MS

NOT for sale

Paper I (General Pathology & Hematology)

1) Cellular Responses to Stress and Toxic Insults:

Paper II (Systemic Pathology)

12) Blood Vessels, 83

There are two kinds of students! Those who utilize their

I believe, great teachers exist, just because of great

Dr. Shiva M.D.

1. Cellular Responses to Stress and Toxic Insults:

1) Tabulate differences between necrosis and degeneration. (Feb. 2017)

II) Connective tissue metaplasia: Formation of mesenchymal elements (cartilage, bone or

II) Liquefactive necrosis

1) Intrinsic (mitochondrial) pathway: Major pathway

Steatosis (Fatty Change)

Mechanisms: Excessive entry or defective metabolism & export of lipids.

Patterns of fatty change

Lipofuscin (Lipochrome or Wear-tear-pigment)

II) Metastatic calcification:

Morphology: Gross Fine white granules or clumps

2. Inflammation and Repair

1) Role of complement in inflammation. (July, 2017)

1) Give four important causes of granulomatous inflammation. (Feb. 2017)

Cardinal Signs of Inflammation

Vascular Events of Acute Inflammation

Complementary Adhesion Molecules

I) Selectins: P-selectin, E-selectin & L-selectin

II) Integrins: ICAM-1, VCAM-1 & PECAM-1

Cell-derived mediators: Vasoactive amines; Arachidonic acid metabolite; Cytokines;

Stimulus: Physical injury; Immediate hypersensitivity reactions; anaphylatoxins

II) Arachidonic acid metabolites (Eicosanoids)

Stimulus: Microbial products

V) Platelet –Activating Factor (PAF)

Source: Platelets, mast cells, neutrophils, macrophages & endothelial cells

VI) Complement system

“Soluble plasma proteins seen in inactive forms, numbered C1 through C9.”

Source: Derived from high-molecular-weight kininogen by the action of enzyme, kallikrein.

Growth Factors Involved in Regeneration and Repair

Healing of Skin Wounds

Healing by Second Intention or Secondary Union

1) Coagulation pathway activation results in formation of a clot covering wound surface.

Factors That Influence Tissue Repair

1) Infection: Delays healing

Complications in Tissue Repair

3. Hemodynamic Disorders, Thromboembolic

a) What is the possible diagnosis?

Ans: Septic shock

a) What is the provisional diagnosis?

Ans: Fat embolism

1) Pathogenesis of septic shock. (July, 2017)

1) Fate of thrombus. (Feb. 2017)

Chronic Passive Hepatic Congestion

Chronic Passive Pulmonary Congestion

Venous Thrombosis (Phlebothrombosis)

Def.: Emboli in the arterial circulation

II) Pulmonary embolism